Effect of nitric oxide synthase inhibitor (L-NAME) on substance P-induced vasodilatation in the dental pulp.

AIM: To investigate the vasodilator mechanisms of pulpal vessels, especially the involvement of nitric oxide (NO), during pulpal inflammation. METHODOLOGY: Eleven cats were prepared for intra-arterial administration of test agents through a lingual artery. The pulpal blood flow was measured by laser Doppler flowmetry from ipsilateral mandibular canine teeth. By using the NO synthase (NOS) inhibitor N(G)-nitro L-arginine methyl ester (L-NAME), the effects of L-NAME on various vasodilators, such as Substance P (SP)-, calcitonin-gene related peptide (CGRP)-, and papaverine-induced vasodilatation, were compared in vivo in 11 feline dental pulps. RESULTS: L-NAME pretreatment potentiates SP-induced vasodilatation for a duration of approximately 5 h. The increase of pulpal blood flow ranged from 91.47 to 109.91%, which was significantly different from SP injection alone (48.79%, P < 0.05). Other vasodilators such as CGRP and papaverine did not respond to L-NAME pretreatment. CONCLUSIONS: This study demonstrates that NOS inhibitor L-NAME administration alone has insignificant effects on pulpal blood flow, although L-NAME pretreatment can potentiate SP-induced vasodilatation, probably via increased activity in the enzyme guanylate cyclase. CGRP and papaverine did not respond to L-NAME pretreatment, indicating that they are not mediated via an endothelium-dependent mechanism.

Microcirculation of a venous flap: an experimental study with microspheres in rabbits.

In recent years, it has been found that maintenance of venous circulation alone may support a small flap with no direct arterial inflow. The clinical application of a venous flap has potential in the field of microsurgery. The purpose of this study was to evaluate the haemodynamics within a pedicled venous flap in rabbits, compared with those of a composite graft. Pedicled venous flaps and composite grafts were raised from the abdominal walls of 30 adult New Zealand rabbits. Flap survival was measured and recorded and blood flow studies with microspheres were done for seven days. The viability of the pedicled venous flaps was much better than that of the composite grafts. At two weeks 24 of the venous flaps (80%) showed more than 75% surviving, but 29 (97%) of the composite grafts had less than 25% surviving. The results suggest that the blood flow through a patent vein maintained in a venous skin flap can provide enough nutrients for the flap to survive during the initial three days until neovascularisation. The venous flap receives more blood flow than a composite graft. We conclude that a venous flap depends on blood supply from the axial vein in addition to neovascularisation to maintain its survival.

Handling 22NaCl by the blood-brain barrier and kidney: its relevance to salt-induced hypertension in dahl rats.

We previously reported that inappropriate renal vasoconstriction in Dahl salt-sensitive (DS) rats fed high NaCl diets may cause sodium retention. The present study examined the distribution and elimination of 22Na in DS and Dahl salt-resistant (DR) rats, and we determined whether an abnormality in renal function might also cause sodium retention in DS rats. Following an intravenous bolus of 4 microCi 22NaCl in prehypertensive DS and DR rats with similar blood pressures on low (0.23%) or high (8% for 4 days) NaCl diets, urinary clearance of 22Na in 1 hour was about 4 times less in DS than DR rats, and renal retention of 22Na was up to 8 times greater in DS than DR rats (P<0.01), suggesting that a renal functional defect may contribute to salt retention in DS rats; however, its uptake in tail artery, heart, lungs, liver, and spleen was similar in DS and DR rats. Uptake in brain was up to 5 times greater in DS than DR rats (P<0.01). Cerebrospinal fluid 22Na radioactivity (in counts per minute) revealed that the blood-brain barrier is 5 to 8 times more permeable to sodium in DS than DR rats (P<0.01). Cerebrospinal fluid volume and brain water content increased significantly (P<0.01) in DS but not DR rats on an 8% NaCl diet. Intracerebroventricular bolus injection of 0.06 mL of 4.5 mol/L NaCl acutely and transiently induced the same degree of hypertension in DR and DS rats, whereas similar volume injections of isotonic saline, 4.5 mol/L Na-acetate, or 4.5 mol/L NaBr did not produce hypertension in either strain. We conclude that functional abnormalities in DS rat kidneys may cause retention of NaCl and that an increased blood-brain barrier permeability to NaCl may enhance its access to sites in the brain that are then activated and induce hypertension.

Impaired renal vasodilation and urinary cGMP excretion in Dahl salt-sensitive rats.

We previously have shown that Dahl salt-sensitive rats increase renal vascular resistance in response to excessive salt feeding before total peripheral resistance increases and hypertension occurs. Failure of renal vasculature to dilate, as normally occurs in Dahl salt-resistant rats fed a high salt diet, may play a role in the development of hypertension in Dahl salt-sensitive rats. We also showed that renal vasculature in salt-sensitive rats is hyperreactive to vasoconstrictors and hyporeactive to vasodilators. Atrial natriuretic peptide, by stimulating cell-bound receptors, and nitroprusside, by generating nitric oxide, cause renal vasodilation by generating cGMP. Studies were undertaken to determine whether defective renal vasodilation in Dahl salt-sensitive rats is due to impaired production of cGMP. We examined the influence of nitroprusside infusion and salt intake on renal vascular resistance and cGMP excretion in salt-sensitive rats. Results demonstrate that salt feeding and nitroprusside infusion increase cGMP excretion and decrease renal vascular resistance in salt-resistant rats (P < .01), and, although this relationship was less clear in salt-sensitive rats, there was a reciprocal relationship between renal vascular resistance and cGMP excretion in all animals studied. Salt feeding and nitroprusside infusion caused less of an increase in cGMP excretion in salt-sensitive than in salt-resistant rats (P < .01). In conclusion, these studies support the concept that impairment in cGMP generation may play a primary role in the inability of the kidneys of Dahl salt-sensitive rats to vasodilate in response to increased salt intake. Such an impairment could contribute to salt retention and the development of hypertension.

Impaired renal vascular reactivity in prehypertensive Dahl salt-sensitive rats.

We have previously shown that renal vascular resistance is less in Dahl salt-sensitive rats than salt-resistant rats fed 1% NaCl diets; however, renal vascular resistance increases before nonrenal vascular resistance as salt-sensitive rats develop hypertension when fed 8% NaCl diets. When salt-resistant rats are given 8% NaCl diets, renal vascular resistance decreases. The current study reports effects of atrial natriuretic peptide, nitroprusside, norepinephrine, angiotensin II, and endothelin-1 on renal and nonrenal vascular resistance in prehypertensive salt-sensitive and salt-resistant rats given 1% NaCl diets; doses used did not affect blood pressure. Resistance of nonrenal vessels in salt-sensitive and salt-resistant rats responded similarly to dilators or constrictors. However, atrial natriuretic peptide and nitroprusside decreased renal vascular resistance of salt-resistant rats (by 65%, p less than 0.01) but not that of salt-sensitive rats. Norepinephrine, angiotensin II, and endothelin-1 increased renal vascular resistance in salt-sensitive rats by 126%, 135%, and 135%, respectively (p less than 0.01); norepinephrine and angiotensin II did not change renal vascular resistance of salt-resistant rats, but endothelin-1 decreased renal vascular resistance in salt-resistant rats by 30% (p less than 0.01). Reactivity of nonrenal blood vessels in prehypertensive salt-sensitive and salt-resistant rats was similar when infused with dilators or constrictors in doses used. By contrast, renal vessels of salt-sensitive rats did not dilate in response to atrial natriuretic peptide and nitroprusside but were hypersensitive to norepinephrine and angiotensin II. Endothelin-1 caused renal vasoconstriction in salt-sensitive rats and renal vasodilation in salt-resistant rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of selected inflammatory mediators on blood flow and vascular permeability in the dental pulp.

One of the major events involving inflammatory processes is the alteration of microcirculatory hemodynamics by inflammatory mediators released from tissue components. Using modern macrocirculatory techniques, 15 mu radioisotope labeled microspheres, 133Xe washout, laser Doppler flowmetry and double isotopes, 125 and 131I-albumin, and microcirculatory methods, intravital fluorescence microscopy with FITC labeled dextran, we have examined the effects of selected mediators, e.g. 5-hydroxytryptamine (5-HT), prostaglandin E2 (PG-E2), bradykinin (BK), substance P (SP), calcitonin gene related peptide (CGRP) and histamine on blood flow and vascular permeability in the pulp of experimental animals. Surprisingly, SP and CGRP caused weak albumin leakage in the pulp, while the opposite is true in high compliance tissues, such as muscles, suggesting that the vessels in a low compliance environment, such as the pulp, may not be as permeable in response to selected mediators. Intraarterial injection of 5-HT caused a strong vasoconstriction which was mediated by 5-HT1p receptor subtype. The pulpal 5-HT receptor subtype was identified by immunocytochemistry, receptor autoradiography and functional investigations. Intravital fluorescence microscopy observations of the rat incisor preparation showed that histamine, BK and PGE2 increased permeability, whereas isoproteranol caused partial inhibition of the BK-induced increase. In an induced pulpal inflammation model using plaque extract, blood flow increased over 40% in the moderately inflamed pulp, which demonstrated severe vasodilation and polymorpholeukocyte accumulation. In the partially necrotic pulp, blood flow decreased nearly 35%. Results of this study clearly show that there is a high structural/functional correlation in pulpal microcirculation in inflammation. As demonstrated in this presentation, the effects of inflammatory mediators on pulpal microcirculatory hemodynamics are complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Dual hemodynamic mechanisms for salt-induced hypertension in Dahl salt-sensitive rats.

Cardiac output, blood volume, total peripheral resistance, and renal blood flow were measured in awake salt-sensitive and salt-resistant Dahl rats on normal rat chow (1% NaCl) and on high salt (8% NaCl) diets. Rats were studied after 4, 8, and 46 weeks on a 1% NaCl diet and after 4 and 8 weeks on an 8% NaCl diet. Salt-sensitive rats on 8% NaCl for 4 weeks developed systolic hypertension; by 8 weeks they developed greater systolic and also diastolic hypertension. Salt-resistant rats on 8% NaCl remained normotensive throughout the studies, although renal resistance decreased (p less than 0.05). At 4 weeks, hypertension in salt-sensitive rats on 8% NaCl was caused by increased blood volume and cardiac output (p less than 0.05), with normal total peripheral resistance. At 8 weeks, hypertension was due to increased total peripheral resistance (p less than 0.05); cardiac output was below normal despite persistent elevation of blood volume (p less than 0.05). Salt-sensitive rats on 1% NaCl for 46 weeks were hypertensive, with elevated total peripheral resistance (p less than 0.05); cardiac output decreased (p less than 0.05), whereas blood volume remained unchanged. Salt-resistant rats on 1% NaCl remained normotensive with no charges in hemodynamics. Salt-sensitive rats on 8% NaCl for 4 weeks had an increase in renal vascular resistance but no significant change in nonrenal resistance or total peripheral resistance. The increased total peripheral resistance in salt-sensitive rats on 8% NaCl for 8 weeks and on 1% NaCl for 46 weeks was a reflection of increases of both renal and nonrenal vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

A double isotope technique to determine regional albumin permeability: effects of anesthesia.

The transvascular leakage of albumin in various organs and tissues was studied with a double isotope technique in rats anesthetized with sodium pentobarbital, given intraperitoneally or intravenously, and in unanesthetized (conscious) rats. 125I-labeled albumin and 131I-labeled albumin were injected into the tail vein 1 hr apart. The albumin permeability index in tissues and organs is indicated by the local ratio (Xa/Ya)/(Xb/Yb), where (Xa/Ya) is the ratio of 125I/131I-albumin activities per g of tissue and (Xb/Yb) is the ratio of 125I/131I-albumin activities per g of blood. If there is no passage of albumin across the capillary membrane over the 1-hr period of study, the permeability index will be equal to one. In unanesthetized rats, the liver, lung, kidney, femoral muscle, and femoral skin were regions with a high albumin permeability index (above 2). In these organs, intraperitoneal and intravenous anesthesia caused a decrease or no significant change of the albumin permeability index. There was no significant albumin leakage over 1-hr period (index not significantly different from 1) in the mesentery, abdominal muscle, abdominal skin, cremaster, heart, and brain of unanesthetized rats. Intraperitoneal anesthesia caused the albumin permeability index to increase to approximately 4 in the mesentery, abdominal muscle, and the abdominal skin, but not in the cremaster, heart, or brain. These results demonstrate that pentobarbital anesthesia when given into the peritoneal cavity causes a significant increase in albumin leakage in the abdominal region.

Effect of verapamil on splanchnic haemodynamics in a portal hypertensive rat model.

To elucidate the effects of verapamil on splanchnic haemodynamics in rats with portal hypertension, verapamil was given at a low dose (0.2 mg/kg) and a high dose (2 mg/kg) to the rat model after portal vein ligation. Approximately 10% decrease in arterial pressure was caused by the low dose of verapamil, with significant decreases in cardiac output and portal venous inflow as well as reduced portal pressure; these were all indicative of a rise in portal vascular resistance. In contrast, the marked fall in both arterial pressure and cardiac output in the high dose, accompanied by a significant decrease in the portal pressure and the unchanged portal venous inflow, suggested a reduction in portal vascular resistance. This study shows that the acute effects of verapamil on portal hypertension may vary with the dosage used. These results also demonstrate that, since the therapeutic efficacy and safety of verapamil is only in a very limited range of dose, caution should be taken in its clinical use in the treatment of cirrhosis with portal hypertension.

Effects of blood viscosity on renin secretion.

The effects of alterations in blood and plasma viscosities on plasma renin activity (PRA) were studied in dogs anesthetized with pentobarbital. Blood viscosity was altered by changing the hematocrit (Hct) level by isovolemic exchange using packed red blood cells or plasma. Plasma viscosity was elevated by isovolemic exchange using Hct-matched blood with high molecular weight dextran (Dx, mean m.w. approximately 450,000) dissolved in plasma. Following control measurements of plasma and blood viscosities, plasma [Dx], PRA, Hct and hemodynamic functions, the dog was subjected to isovolemic exchange transfusions to either alter the Hct or administer the Dx. Various measurements were repeated 40-60 min after each exchange. Arterial pressure and renal blood flow remained relatively constant after exchanges; increases in plasma and blood viscosities were accompanied by a decrease in renal vascular hindrance (vasodilation) to keep the renal flow resistance at control level. PRA rose with increases in plasma [Dx] and viscosity, and the rise in PRA was best correlated with the decrease in renal hindrance. The changes in PRA and renal hindrance have the same regression line whether blood viscosity was altered by Hct variation or Dx administration. The results indicate that increases in viscosity cause a compensatory vasodilation of renal vessels to cause renin secretion.

An animal study of portal hypertension.

For the purpose of elucidation the mechanism of portal venous resistance and portal venous blood flow in maintaining an elevated portal hypertension. The splanchnic and systemic hemodynamics were evaluated in portal hypertensive rat model, which is induced by partial portal vein ligation (PVL). Organ blood flow and portal-systemic shunting were measured by radio-active microsphere techniques. In this study all the PVL rats had higher mean portal venous pressure (15.2 +/- 1.6 mmHg) when compared to the Sham-operation control rats (5.3 +/- 1.2 mmHg). Furthermore, portal systemic shunting was significantly higher in the 14th day PVL rats (87.2 +/- 3.6%) than control rats (0.3 +/- 0.1%) (p less than 0.05). There was a rapid increase in portal venous inflow from the 4th day (6.1 +/- 0.8 vs 4.2 +/- 0.7 ml/min/100 gm BW, p less than 0.05) in the PVL rats than in control rats. However, the total peripheral resistance and splanchnic arterial resistance were reduced in the 14th PVL rats than control rats. The Cardiac index was much higher in the 14th PVL rats than control rats. Thus our results demonstrate that portal hypertension is maintained by a hyperdynamic portal venous inflow. This model is reproducible for us to study portal hypertension within a short period of time.

Salt-induced hypertension in Dahl salt-sensitive rats. Hemodynamics and renal responses.

This study was performed with Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats to detect differences in cardiovascular hemodynamics and renal responses that might be involved in initiating salt-induced hypertension in DS rats. The effects of 4 weeks of 8% NaCl diet were studied in conscious, male DR and DS rats in which vascular and urinary catheters had been previously implanted. Results were compared with those obtained from control groups of DR and DS rats on 4 weeks of 1% NaCl diet. DR rats on 8% salt diet did not develop hypertension, and cardiac output and blood volume were unchanged; glomerular filtration rate, urinary flow, sodium excretion, and plasma atrial natriuretic factor (ANF) increased. DS rats on 8% salt diet developed hypertension, and cardiac output and blood volume increased; glomerular filtration rate, urinary flow, and sodium excretion did not change, despite an increase in ANF. DS and DR rats on 1% NaCl diet were subjected to ANF infusion. After ANF infusion DR rats had a decreased blood volume and an increased glomerular filtration rate, urinary flow, and sodium excretion; DS rats showed no significant changes in blood volume, glomerular filtration rate, urinary flow, or sodium excretion. ANF caused vasodilation in all regions studied in DR rats; DS rats showed vasodilation in all regions except the kidney. After acute volume expansion, although both DR and DS rats responded by an increase in cardiac output, only DS rats developed prolonged hypertension. This finding suggests an inadequate vasodilatory mechanism in DS rats. In response to acute volume expansion, renal resistance decreased in DR rats but not in DS rats. It is concluded that the primary hemodynamic disturbance in DS rats with salt-induced hypertension is an increase in cardiac output caused by blood volume expansion in the absence of any vasodilation. Comparison of the responses of DS and DR rats to high salt diets, ANF infusion, and acute volume expansion indicates that the salt-induced hypertension in DS rats is initiated by a diminished renal response to ANF.

Effects of dextran-induced hyperviscosity on regional blood flow and hemodynamics in dogs.

In 10 pentobarbitalized dogs, plasma viscosity (Ep) was raised fourfold while apparent blood viscosity (Ea) increased about twofold by two steps of exchange transfusion of 200 ml of plasma with plasma containing high molecular weight dextran (mol wt 500,000, 20% wt/vol). Elevation of Ea was primarily caused by an increase of Ep but not red cell aggregation. As Ea increased, regional blood flow (by 15-microns microspheres) remained constant in most organs but reduced in the small intestine, spleen, and thyroid gland. Vascular hindrance (Z), which reflects the state of vascular geometry, was calculated as flow resistance per Ea. Among various organs, a reduction in Z was noted in the heart, liver, pancreas, kidney, brain, and adrenal gland. In myocardium, there was a progressive reduction of the endocardial-to-epicardial flow ratio, indicating a less profound vasodilation in endocardium than epicardium. These results indicate that dextran-induced hyperviscosity leads to a compensatory vasodilation in several vital organs thus serving to maintain blood flow and nutrient transport.

Dependence of technetium-99m red blood cell labeling efficiency on red cell surface charge.

The mechanisms by which [99mTc]pertechnetate becomes attached to stannous-primed red blood cells are not known in detail. To study the problem further, the effect of red cell surface charge on labeling efficiency was evaluated. Red cell surface charge was reduced by using the enzyme neuraminidase to remove the terminal charge-bearing sialic acid moiety of the membrane glycoprotein. Forty-five blood samples from six volunteers were treated with neuraminidase for varying lengths of time, resulting in the removal of from 11% to 99% of the normal negative surface charge, as determined from electrophoretic mobility measurements. There was excellent linear correlation between labeling efficiency and the remaining red cell surface charge for values down to 20% of normal (r = 0.89). When surface charge was less than 20% of normal, labeling efficiency was constant at 30%. Eleven blood samples from three donors were divided into two groups that were treated with neuraminidase either before or after they were labeled. The labeling efficiency was independent of the order in which the steps were performed. No evidence for shifting of the radiolabel from the cell membrane to hemoglobin was found. The results suggest that clinical conditions associated with a reduction of sialic acid on the erythrocyte membrane may be one cause of decreased red blood cell labeling efficiency, and that increased membrane permeability for reduced technetium species may be responsible for the decrease.

Studies on sequestration of neuraminidase-treated red blood cells.

The effects of reduction in the surface charge of red blood cells (RBCs) on regional blood flow and RBC distribution were studied in rats anesthetized with pentobarbital sodium. RBCs were treated with neuraminidase to reduce their electrophoretic mobility by 56%. Normal and neuraminidase-treated RBCs labeled with 51Cr or 111In were injected into a femoral vein while an equal volume of blood was simultaneously withdrawn from a femoral artery. More than 70% of the neuraminidase-treated RBCs injected disappeared from the circulating blood in 30 min compared with less than 2% of normal RBCs. The relative distributions of neuraminidase-treated RBCs to normal RBCs, as determined from radioactivity counting, were significantly greater than 1 in the spleen (5.65 +/- 0.97, mean +/- SD), the liver (2.84 +/- 0.21), the lung (1.48 +/- 0.31), and the kidney (1.49 +/- 0.27), indicating a preferential trapping of neuraminidase-treated RBCs in these regions. This ratio was approximately 1 in all other organs. Regional blood flows in tissues were determined with 15-micron microspheres in the control period and after the infusion of neuraminidase-treated RBCs (experimental). Experimental-to-control blood flow ratios were 0.40 +/- 0.05 in the spleen, 0.66 +/- 0.06 in the liver, 0.78 +/- 0.03 in the lung, and 0.78 +/- 0.09 in the kidneys; this ratio was approximately 1 in all other organs. An experimental-to-control blood flow ratio less than 1 indicates a reduction in blood flow; this occurred in the same organs as those with trapping of neuraminidase-treated RBCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of reduced red cell deformability on regional blood flow.

The effects of a reduction in red blood cell (RBC) deformability on regional blood flow and RBC distribution were studied in rats anesthetized with pentobarbital sodium. RBCs were subjected to minimum hardening by incubation in a very diluted solution of glutaraldehyde (0.025%). Normal and partially hardened RBCs, labeled with 51Cr or 111In, were injected into the femoral vein, while an equal volume of blood was simultaneously withdrawn from the femoral artery. Approximately 70% of the labeled, partially hardened RBCs disappeared from the circulating blood within 25 min after injection, compared with less than 2% of the labeled normal RBCs. The relative distribution of RBCs with reduced deformability to normal RBCs in tissues was determined from radioactivity counting; this ratio (mean +/- SD) was 7.95 +/- 0.85 in the spleen, 7.44 +/- 0.43 in the sternum, 7.10 +/- 1.09 in the lung, 4.54 +/- 0.31 in the liver, and 3.50 +/- 0.61 in the femur bone. The results indicate a significant degree of trapping of RBCs with reduced deformability in these regions. This ratio of relative distribution of RBCs with reduced deformability as compared with normal RBCs was 1.06 +/- 0.13 in the heart, indicating the absence of preferential trapping of RBCs with reduced deformability in this organ. Regional blood flows were determined with 15-microns microspheres in the control period and after infusion of RBCs with reduced deformability (experimental).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of blood viscosity on plasma renin activity and renal hemodynamics.

The effects of alterations in apparent blood viscosity on renal hemodynamics and plasma renin activity (PRA) were studied in dogs anesthetized with sodium pentobarbital. Blood viscosity was altered isovolemically either by changes in hematocrit (Hct) or by an increase in plasma viscosity (dextran administration). Arterial blood pressure and renal blood flow (RBF) remained relatively constant when apparent blood viscosity was elevated by changes in Hct or plasma viscosity. Thus the hyperviscosity of blood was associated with a decrease of renal vascular hindrance, resulting in an essentially unchanged renal flow resistance. The decrease in renal vascular hindrance may result from renal vasodilation. In hyperviscosity induced with dextran, the increase in PRA correlates linearly with the decrease in renal vascular hindrance, with a coefficient of correlation of 0.968 (P less than 0.005). The increase in PRA that resulted when Hct was raised from 25 to 55% also can be correlated linearly with the decrease in renal vascular hindrance, with a coefficient of correlation of 0.953 (P less than 0.005). These results suggest that the decrease in renal vascular hindrance in response to a rise in apparent blood viscosity leads to an increase in PRA.

Effects of experimental hypotension on hemodynamics and renin secretion rate.

The effects of hypotension on systemic and renal hemodynamics, plasma renin activity (PRA), and renin secretion rate (RSR) were determined in dogs anesthetized with sodium pentobarbital plus chloralose. Renal blood flow (RBF) was determined with microspheres (15 micron) and with an electromagnetic flowmeter connected to an extra-corporeal circuit from the femoral artery to the renal artery. Hypotension was induced by nitroprusside infusion, which decreased peripheral resistance, and by hemorrhage, which reduced cardiac output. RSR increased in both forms of hypotension, but the increase following hemorrhage was greater than that after nitroprusside. Thus, when the mean arterial pressure (MAP) was reduced to 75 mmHg, RSR increased from 470 +/- 26 units/min to 990 +/- 12 units/min with nitroprusside and from 415 +/- 13 units/min to 1,509 +/- 21 units/min following hemorrhage. At MAP of 50 mmHg, RSR increased to 1,541 +/- 64 units/min with nitroprusside and to 2,254 +/- 98 units/min following hemorrhage. Nitroprusside increased renin secretion not only by an increase in sympathetic beta adrenergic activity through the baroreceptor reflex, but also by its direct vasolidatory effect in the renal circulation. In hemorrhagic hypotension, the increase in renin secretion was accompanied by renal vasoconstriction. The greater increase in RSR following hemorrhage than after nitroprusside at given levels of hypotension may be explained by a stronger beta adrenergic activation, the activation of prostaglandin and kallikrein systems, a lower microvascular pressure level, and/or smaller pulse pressure and lower sodium load in the macula densa. The comparison of renin secretion at the same degree of hypotension induced by different hemodynamic alterations serves to elucidate the mechanisms of renin secretion.

Regional cerebral blood flow and oxygen consumption of the canine brain during hemorrhagic hypotension.

The sequential changes in systemic and cerebral hemodynamics, systemic and cerebral oxygen transport and consumption rates, and the regional blood flows (measured with 15 micron microspheres) to the cortical and subcortical brain tissues were determined in nine dogs subjected to graded hemorrhage (10 ml/kg X 4 at 15 min intervals). As hemorrhage progressed, both mean arterial pressure and cardiac output decreased progressively. In contrast to the systemic circulation, the mean cerebral blood flow (mCBF) was well maintained by cerebral vasodilation and the cerebral O2 consumption rate (CMRO2) increased during the first three stages of hemorrhage. At 40 ml/kg of hemorrhage, there were significant reduction in mCBF and CMRO2 despite the increase in O2 extraction, suggesting the occurrence of cerebral hypoxia and decompensation of the cerebral circulation. There were remarkable regional variations in the responses of regional cerebral blood flows (rCBF) to hypovolemia, resulting in a significant redistribution of cerebral blood flow. The fractions of cardiac output supplying the diencephalon (thalamus and hypothalamus), the brain stem (pons and medulla oblongata) and the cervical spinal cord increased after hemorrhage up to 40 ml/kg. The redistribution of rCBF favors those areas where neurons related to cardiovascular control are located. These findings have significant implications relating to hemodynamic regulation during hemorrhagic hypotension.

Effects of variations in renal hemodynamics on the time course of renin secretion rate.

The effects of variations in renal hemodynamics on the time course of renin secretion were studied in dogs anesthetized with pentobarbital-chloralose. Hemodynamic changes were induced either locally in kidneys perfused in situ via an extracorporeal circuit (with or without a pump system) or systemically by hemorrhage or nitroprusside infusion. In the autoperfused kidney the reduction of renal perfusion pressure to approximately one-half of the arterial pressure by inflow occlusion caused an increase in renal conductance (renal vasodilation) and an increase in renin secretion rate (RSR). In the pump-perfused kidney, a step increase in renal blood flow (RBF) caused renal vasoconstriction and a decrease in RSR; a step decrease in RBF caused renal vasodilation and an increase in RSR. Following step changes in RBF, the time constant of the alterations of renal conductance was 56.5 s, and the time constant of the RSR responses was 80.1 s. The total time required to reach a steady state for RSR lagged behind that for renal conductance by approximately 5 min. These differences reflect the time needed for the kidney to release renin in response to changes in renal vascular caliber. The results suggest that renin release occurs in response to the autoregulatory dilation of the renal arterioles. When systemic hypotension was induced by nitroprusside infusion, RSR also increased together with the renal conductance. Following hemorrhage, however, RSR increased despite a decrease in renal conductance, reflecting the role of neurohumoral factors in causing renin release in this case. The comparison of renin secretion following different types of hemodynamic alterations serves to elucidate the mechanisms of renin secretion.