Effects of acetaminophen and ibuprofen on renal function in anesthetized normal and sodium-depleted dogs.

In certain conditions, renal prostaglandins (PGs) are important determinants of kidney function. Under these "renal PG-dependent states," pharmacological inhibition of vasodilatory PG may result in excessive renal vasoconstriction and adversely affect kidney function. The purposes of this study were to determine whether acetaminophen (Acet), a weak PG-synthesis inhibitor, influences kidney function in the renal PG-dependent state of anesthesia and sodium depletion. Comparisons were made with ibuprofen (Ibu). Measurements of PGE2 excretion were used to assess renal PG synthesis. Acet (15 mg/kg) and Ibu (10 mg/kg) both decreased renal blood flow and glomerular filtration rate by approximately 20-30% in normal, anesthetized, sodium-replete dogs. Although Acet produced similar changes in renal blood flow and glomerular filtration rate in the low-sodium dogs, Ibu caused a significantly greater renal vasoconstriction (64 +/- 10%) in these animals. Both Acet and Ibu inhibited urinary PGE2 excretion in sodium-replete and low-sodium dogs. Ibu tended to have a greater and more prolonged effect than did Acet. These results suggest that Acet alters PGE2 excretion and kidney function under renal PG-dependent conditions; the effects, however, are less severe than those seen with Ibu.

Effects of acetaminophen and ibuprofen on renal function in the stressed kidney.

Exercise, salt restriction, and/or dehydration causes transient reductions in renal function that may be buffered by vasodilatory prostaglandins (PGs). Over-the-counter (OTC) analgesics have the potential to alter renal hemodynamics by inhibiting renal PGs. Therefore, we tested the renal effects of the maximal recommended dose of acetaminophen (Acet, 4 g/day) and ibuprofen (Ibu, 1.2 g/day) vs. a placebo (Pl) in humans subjected to progressive renal stresses. After baseline measurements, 12 fit young (25 +/- 1 yr) men and women underwent 3 days of a low (10 meq/day)-sodium diet while taking one of the drugs or Pl (crossover design). Day 4 involved dehydration (-1.6% body wt) followed by 45 min of treadmill exercise (65% maximal O2 uptake) in the heat (36 degreesC). These combined stressors caused dramatic decreases in effective renal plasma flow, glomerular filtration rate (GFR), and sodium excretion. Baseline GFR (range: 118-123 ml/min) decreased to 78 +/- 4, 73 +/- 5, and 82 +/- 5 ml/min postexercise in the Acet, Ibu, and Pl trials, respectively, with a significantly greater decrease in GFR in the Ibu trial (P < 0. 05 vs. Pl). OTC Ibu has small but statistically significant effects on GFR during exercise in a sodium- and volume-depleted state; OTC Acet was associated with no such effects.

Nitric oxide inhibition causes an exaggerated pressor response in Yucatan miniature swine.

The involvement to nitric oxide (NO) in cardiovascular and renal function was evaluated in 12 anesthetized Yucatan miniature swine. The effect of NO blockade on blood pressure was measured in six additional conscious swine. In the anesthetized swine, mean arterial pressure (MAP), heart rate, glomerular filtration rate (GFR), and urinary excretion of water, sodium, and potassium were measured after systemic inhibition of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME), and were compared with values for a control period. After NO synthesis blockade, MAP increased by 63 +/- 5 mm Hg, a far greater increase than those observed in rats, dogs, domestic swine, or humans. The changes in GFR, urine flow rate (UFR), and sodium excretion (UNaV) were time-dependent. The GFR decreased to 50 +/- 6% of control values immediately after L-NAME administration, but returned to control values within 1 h. Significant increases in UFR and UNaV were observed only during the third experimental period, 40 to 60 min after drug infusion. In the conscious swine, L-NAME administration increased MAP by 24 +/- 4 mm Hg. Administration of the sympatholytic hexamethonium bromide fully reversed the increase of MAP in anesthetized and conscious swine. These findings indicate that NO has an important role in the maintenance of cardiovascular and renal function in Yucatan miniature swine. The exaggerated pressor response to NO blockade in miniature swine appears to involve the sympathetic nervous system.

Nitric oxide attenuates the renal hemodynamic responses to increased peripheral and renal sympathetic nerve activity.

The role of nitric oxide (NO) in renal function was evaluated under conditions of elevated peripheral and renal sympathetic nerve activity (RSNA), achieved by bilateral carotid occlusion (CO) in anesthetized dogs. Renal function was monitored during CO with the NO system intact and with it blocked by the administration of L-NAME. With NO intact, CO increased arterial pressure and heart rate. With renal perfusion pressure held constant, CO also significantly decreased renal blood flow (RBF) and glomerular filtration rate (GFR) by 46% and 43%, respectively. CO, after L-NAME administration, resulted in a significantly exaggerated renal vasoconstriction. RBF and GFR decreased by 82% and 80%, respectively. Changes in water and sodium excretion were not different between the NO-intact and NO-blocked states during CO. These studies were also performed with the converting enzyme inhibitor, Captopril. The exaggerated renal hemodynamic responses to CO with NO synthesis inhibition were identical with or without Captopril. These findings indicate that under conditions of elevated peripheral and RSNA, NO plays an important role in modulating renal hemodynamics, but not sodium excretion. This effect does not appear to involve angiotensin II.

The effects of nonsteroidal anti-inflammatory drugs on renal function: experimental studies in animals.

Studies in various experimental animal models have been invaluable in delineating the physiological and pathophysiological conditions under which renal prostaglandin (PG) synthesis is a major determinant of renal function; conditions in which the inhibition of renal PG synthesis by the administration of a nonsteroidal anti-inflammatory drug (NSAID) will significantly alter kidney function. This article presents the initial schema or concept that under certain well-defined conditions or disease states, an increase in renal sympathetic adrenergic and/or angiotensin II activity stimulates an increase in the synthesis of vasodilatory PG (PGE2/PGI2) to offset or modulate the vasoconstriction. In these renal "PG-dependent" states, a reduction of renal PG by NSAID administration adversely affects renal function by causing renal vasoconstriction, thus decreasing glomerular filtration and causing the retention of sodium and water. More recent experimental data from animal models are then reviewed to illustrate that the number of conditions or disease states in which renal function is PG-dependent has increased dramatically. Last, evidence is reviewed suggesting that under certain conditions, inherent increases in the synthesis of renal vasodilatory PGE2 and PGI2 and/or vasoconstrictive thromboxane A2 (TxA2) may be occurring. In these situations, renal function would also be more susceptible to NSAID-induced renal vasoconstriction and sodium retention.

Indomethacin attenuates exercise-induced proteinuria in hypertensive miniature swine.

Exercise-induced proteinuria may be increased in hypertensives. The mechanisms underlying the increased proteinuria are not known, and it has not been determined whether animal models of hypertension exhibit a similar response. We investigated whether indomethacin (Indo) altered exercise-induced proteinuria in normal and hypertensive deoxycorticosterone acetate (DOCA) Yucatan miniature swine (YMS). Five normal and four DOCA YMS underwent 30 min of treadmill exercise at 80% of maximal heart rate. Cumulative (exercise + recovery) albumin excretion in the DOCA YMS was 25-fold (P < 0.01) greater than observed in the normal YMS. Indo had no effect on resting or exercise-induced proteinuria in the normal YMS. However, Indo decreased the slightly elevated proteinuria at rest, and normalized the exaggerated exercise-induced proteinuria in the DOCA YMS. The antiproteinuric effect of Indo in the DOCA YMS was not associated with altered exercise, recovery blood pressure, or glomerular filtration rate. Thus hypertensive DOCA YMS exhibit an exaggerated exercise-induced proteinuria. It is suggested that eicosanoids are involved in this abnormal renal proteinuric response to exercise.

Exercise-induced proteinuria is attenuated by indomethacin.

The role of the prostaglandin (PG) and renin-angiotensin hormonal systems in exercise-induced proteinuria following 30 min of submaximal, steady-state exercise was evaluated. Eight healthy males performed cycle ergometry at 75% of VO2peak on three occasions after the administration of a placebo (PLACEBO), a prostaglandin inhibitor (indomethacin, INDO), and an angiotensin converting enzyme inhibitor (captopril, CAPTO). Urine and blood samples were collected prior to, immediately following exercise, and over 40-min recovery. Data were evaluated for differences among drug treatments and measurement phases. During PLACEBO, exercise increased total protein excretion from 64.9 +/- 9.5 to 408.6 +/- 160.8 micrograms.min-1 (P < 0.05). PG inhibition with INDO significantly attenuated the increased proteinuria due to exercise (149.2 +/- 64.0 micrograms.min-1). The proteinuric response to exercise was not altered by CAPTO. Resting plasma renin activity (PRA) and aldosterone (ALDO) were significantly reduced during the INDO trial. Although the twofold increment in ALDO with exercise remained intact during the INDO trial, the PRA response to exercise was significantly blunted. No treatment differences were observed for mean arterial pressure, sodium excretion, urine flow, or creatinine clearance values during rest or exercise. These results suggest that the proteinuria associated with steady-state exercise is PG dependent and not related to hemodynamic influences.

Acute renal function in chronically sympathectomized deoxycorticosterone acetate-treated miniature swine.

We recently validated a swine model in which chronic treatment with 6-hydroxydopamine (6-OHDA) produced an effective sympathectomy. These sympathectomized swine demonstrated a significantly attenuated hypertensive response when treated with deoxycorticosterone acetate (DOCA). Because renal nerve activity is elevated and important in controlling renal function and blood pressure in the DOCA swine model, we wanted to study the effect of chronic sympathectomy on acute renal hemodynamics and tubular function. Kidney function was assessed in 14 DOCA-treated miniature swine, 8 of which were sympathectomized by chronic treatment with 6-OHDA, while 6 served as controls. Effective renal sympathectomy in this model has been previously confirmed by a significant reduction (97%) of norepinephrine in renal cortical tissue. When anesthetized, mean arterial pressure and renal blood flow were similar between the two groups. Glomerular filtration rate was lower by 43%, urine flow rate by 71%, sodium excretion by 66%, and potassium excretion by 48% in the 6-OHDA DOCA animals. All of these parameters were significantly different from the intact DOCA controls. These results indicate that anesthetized, chronically sympathectomized swine exhibit decreased renal excretory function. The changes in renal function may have been due to the development of a tubular or glomerular supersensitivity to circulating antinatriuretic factors, since the 6-OHDA group had a 28% greater pressor response to the alpha-agonist phenylephrine and a significantly greater fall in mean arterial pressure in response to alpha-blockade with prazosin when compared with the controls. These changes in renal function may also explain why the 6-OHDA animals demonstrated a slight increase in mean arterial pressure in response to DOCA. Because acute renal denervation in DOCA-treated swine produces a diuresis and natriuresis, this study affirms that there may be important functional differences in acutely versus chronically denervated kidneys for which the implications under normal physiologic conditions are unknown.

Chemical sympathectomy alters the development of hypertension in miniature swine.

To determine if the neurotoxin 6-hydroxydopamine could be used to chemically sympathectomize neonatal miniature swine, eight newborn swine were treated with 6-hydroxydopamine beginning on the first day after birth and continuing at regular intervals for the next 6 months. Six littermates served as controls and received vehicle injections. A significant reduction in the pressor response to intravenous tyramine (95%) and in the tissue norepinephrine content of the kidneys, left ventricle, and gastrocnemius muscle (more than 93%) provided evidence for an effective long-term sympathectomy in the 6-hydroxydopamine-treated animals. In addition, the blood pressure response of these young, chemically sympathectomized swine to chronic deoxycorticosterone acetate treatment was evaluated. Mean arterial pressure before deoxycorticosterone was similar in the 6-hydroxydopamine-treated (116 +/- 2 mm Hg) and control (125 +/- 5 mm Hg) groups. One week after deoxycorticosterone, mean arterial pressure had risen significantly by 20-22 mm Hg in both groups. Blood pressure continued to increase in the control group, reaching a value of 163 +/- 6 mm Hg by the third week after treatment. In contrast, mean arterial pressure in the 6-hydroxydopamine group did not increase further during weeks 2 and 3 after deoxycorticosterone. In conclusion, chronic treatment of neonatal swine with 6-hydroxydopamine produced an animal model with an effective, general, peripheral sympathectomy. The significant attenuation of the hypertensive response in these sympathectomized animals lends further support to the hypothesis that an intact sympathetic nervous system is necessary for the full expression of deoxycorticosterone hypertension in miniature swine.

Renal denervation decreases blood pressure in DOCA-treated miniature swine with established hypertension.

The role of renal sympathetic nerve activity (RSNA) in the maintenance phase of essential hypertension has not yet been clearly defined. Renal function and mean arterial pressure (MAP) were studied in four Yucatan miniature swine (YMS) with established DOCA hypertension prior to and for 3 weeks after surgical renal denervation (RDX). During the first week post-RDX, MAP decreased from 141 /+- 6 to 121 +/- 3 mm Hg (P less than .05), while sodium balance increased from 0.32 +/- 0.05 to 0.95 +/- 0.14 mEq/kg/day (P less than .05). By 3 weeks post-RDX, MAP remained below normotensive levels while sodium balance returned to the pre-RDX value. There was no significant change in potassium or water balance after RDX. Thus, in DOCA-YMS the renal nerves are important in the maintenance of hypertension. The reduction in MAP with RDX in the absence of a natriuresis suggests a role for renal afferent nerve activity.

Effects of 6-hydroxydopamine in hypertensive adult miniature swine.

To validate a miniature swine model of sympathectomy, six swine that had chronic high blood pressures for unknown reasons and five DOCA hypertensive swine were treated with a single dose of the neurotoxin 6-hydroxydopamine (6-OHDA) (50 mg/kg i.v.). One week after 6-OHDA, conscious mean arterial pressure (MAP) had fallen by 47-49 mmHg and the pressor response to tyramine was attenuated in both groups. Norepinephrine content was significantly decreased in the kidneys (greater than 85%) and left ventricle (greater than 94%) in both 6-OHDA treated groups. These results indicate that 6-OHDA can be used to effectively sympathectomize adult swine. Chemical sympathectomy of swine with either unexplained high blood pressure or experimentally induced DOCA hypertension resulted in an equivalent fall in MAP in both of these populations. Further studies using 6-OHDA in miniature swine may help to elucidate the mechanisms involved in maintaining hypertension in this animal model.

Renal nerves in renal sodium-retaining states: cirrhotic ascites, congestive heart failure, nephrotic syndrome.

The focus of this review is on the role of the renal nerves in contributing to the sodium retention associated with cirrhosis, congestive heart failure, and nephrotic syndrome. With respect to these three disease state information is presented which indicates that conditions exist which would be predicted to activate the sympathetic nervous system. Consistent with this, indirect indices of increased peripheral and renal sympathetic nerve activity are observed in these diseases. Acute experiments have indicated that the renal nerves are influencing sodium excretion in these sodium-retaining disorders. The renal nerves have the capacity to influence tubular sodium transport, renal hemodynamics, and renal endocrine release, all of which may affect the renal handling of sodium. Experiments are discussed which have implicated all three mechanisms of action in cirrhosis and congestive heart failure. Despite the fact that studies are demonstrating an increasing importance of the renal nerves, experiments have not been conducted to definitively implicate the renal nerves as being responsible for the long-term sodium retention in these disease conditions.

Salicylic acid causes a diuresis and natriuresis in normal and common bile-duct-ligated cirrhotic miniature swine.

In patients with liver disease, or in normal subjects who are sodium-depleted, the administration of either a nonsteroidal anti-inflammatory drug or acetylsalicylate (aspirin) has a detrimental effect on the kidney; profound renal vasoconstriction and the retention of sodium and water may occur. We observed recently that salicylate (SA), in contrast to meclofenamate (MECLO) or aspirin, caused a diuresis and natriuresis in the sodium-depleted dog. To determine if SA would similarly affect the kidneys in a cirrhotic subject, the effects of SA (40 mg/kg) and subsequent MECLO treatment (2 mg/kg) were evaluated in five normal and six common bile-duct-ligated (CBDL) miniature swine. All six CBDL animals showed signs of biliary cirrhosis and four of the six were ascitic at the time of study. SA did not significantly alter renal blood flow or glomerular filtration rate in either the normal or CBDL animals. In both groups, SA caused a significant diuresis and natriuresis. MECLO, given after SA, caused a reduction in renal blood flow in the normal but not in the CBDL animals, but did not alter glomerular filtration rate in either group. In the CBDL animals, when MECLO was given alone a significant decrease in renal blood flow occurred. MECLO abolished the SA-induced diuresis and natriuresis in the normal swine but only affected the SA-mediated natriuresis in the CBDL animals. SA significantly reduced renal prostaglandin E2 excretion in both groups. With MECLO, prostaglandin E2 excretion was reduced further in the normals but not in the CBDL animals. These data demonstrate that SA does not produce detectable renal vasoconstriction in the cirrhotic pig.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of salicylate vs. aspirin on renal prostaglandins and function in normal and sodium-depleted dogs.

The effects of aspirin (acetylsalicylate) (ASA) and nonsteroidal antiinflammatory drugs (NSAIDs) on renal prostaglandin (PG) biosynthesis and function have been studied extensively. In contrast, the in vivo effects of a nonacetylated salicylate (SA), such as sodium SA, on renal function have not been well characterized. No studies have examined the effects of SA on renal function in a situation in which the maintenance of normal kidney function is dependent upon intact renal PG synthesis (i.e., sodium restriction-elevated plasma renin activity). To evaluate the effects of SA vs ASA and/or a NSAID, normal and sodium-restricted anesthetized dogs were treated with SA and then meclofenamate (MECLO) or ASA followed by MECLO. In the normal animals, SA significantly decreased renal PGE2 and PGF2 alpha excretion. After SA a significant amount of MECLO-suppressible PGE2 and PGF2 alpha synthesis remained intact. Compared to SA, with ASA there was a greater decrease in PG excretion, with no further decrease in PG excretion with subsequent MECLO treatment. In the sodium-restricted animals (plasma renin activity, 18-24 ng of angiotensin l/ml/hr) ASA decreased PGE2 excretion but SA did not. In these animals SA did not cause renal vasoconstriction. Additional groups of sodium-restricted animals were studied with extremely high doses of ASA and SA (90 mg/kg) to elevate plasma SA to 200 to 250 micrograms/ml. In these animals SA did decrease PGE2 excretion significantly, but only to levels seen typically in normal animals and, after SA, a large amount of PGE2 excretion could be suppressed by MECLO.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chronic hyperoxia on the cardiovascular responses to vasoactive compounds in the rabbit.

This study evaluated the effect of hyperoxia on the pharmacokinetic function of the lung. Hyperoxia is known to disrupt the activities of the pulmonary prostaglandin dehydrogenase/reductase and angiotensin converting enzymes. This would be predicted to alter the activation/deactivation of prostaglandins or angiotensin. The ability of these enzyme systems to act upon these compounds was evaluated by measuring the changes in the peripheral vascular responses to exogenous prostaglandin and angiotensin. Two groups of conscious, chronically catheterized rabbits, one exposed to ambient air and the other to greater than 98% oxygen, were given bolus injections of angiotensin I, angiotensin II, prostaglandin E2, sodium nitroprusside, and phenylephrine before and during up to 88 h of air or oxygen exposure. The hyperoxic animals' responsiveness to angiotensin I and angiotensin II decreased by 47% and 55%, respectively, after 72 h of oxygen exposure. The hyperoxic animals demonstrated a 54% increase in the vasodilatory response to arterial prostaglandin E2. Normoxic rabbits demonstrated no changes in response to any of the compounds tested. These data indicate that chronic hyperoxia influences either the synthesis/degradation and/or vascular receptors to both angiotensin I and II and prostaglandins.

Effects of aortic constriction and renal denervation in DOCA-hypertensive swine.

The autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) was examined in normal and deoxycorticosterone acetate (DOCA)-hypertensive Yucatan miniature swine (YMS). Aortic constriction (AC) was used to vary renal perfusion pressure (RPP) from 158 to 90 mmHg for DOCA-YMS and 124 to 50 mmHg for normals. DOCA animals had calculated RBF autoregulatory indexes demonstrating less effective autoregulation compared with controls. Over the pressure range of RBF autoregulation, control animals also autoregulated their GFR, whereas most DOCA animals did not. When renal function in DOCA-YMS was evaluated at the normotensive RPP of 115 mmHg, GFR, urine volume, and sodium excretion were decreased by approximately 60, 70, and 80%, respectively. In DOCA-YMS, after the normalization of RPP to 115 mmHg, renal denervation significantly increased RBF. In DOCA animals the relative decrease in sodium and water excretion in relation to decreased RPP was not altered by renal denervation. In this hypertensive model the excretion of water and sodium are closely linked to RPP. At a normotensive RPP the sodium retention in the DOCA animals may be even further exaggerated by their inability to autoregulate GFR.

Renal prostaglandin E2 and F2 alpha synthesis during exercise: effects of indomethacin and sulindac.

To assess the effects of acute exercise on renal prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) synthesis, urine collections were obtained from six women before and after 30 min of treadmill exercise at approximately 80% of their maximal oxygen consumption. After receiving a placebo for 3 days, with acute exercise, there was a significant increase only in recovery urine PGE2 concentration. Due to a decline in urine volume, PGF2 excretion was unchanged and PGF2 alpha excretion was significantly decreased by exercise. Subjects repeated the tests after 3 d of indomethacin treatment (150 mg X d-1), a known renal prostaglandin (PG) inhibitor, and 3 d of sulindac (300 mg X d-1), a non-steroidal anti-inflammatory drug which may not inhibit renal PG synthesis. Pre-exercise urine PGE2 concentrations were decreased by indomethacin but not by sulindac, whereas, PGF2 alpha concentrations were decreased by both drugs. When compared to the control test, indomethacin and sulindac had different effects on pre-exercise urine/plasma osmolality ratios and free water clearances. Neither indomethacin nor sulindac influenced the decreases in free water clearances, which were observed during the placebo tests. Exercise proteinuria was significantly increased by indomethacin but not by sulindac. In conclusion, these data demonstrate that acute exercise may stimulate renal PGE2 synthesis. During exercise, renal PG synthesis attenuates protein excretion. There also appear to be differences between indomethacin and sulindac with regard to the effects on renal PG synthesis and kidney function.

Effects of acute renal denervation on kidney function in deoxycorticosterone acetate-hypertensive swine.

Deoxycorticosterone acetate-induced hypertension in Yucatan miniature swine appears to involve elevated peripheral sympathetic activity. Abnormalities in renal function in these hypertensive animals are also apparent. To determine the extent to which renal nerve activity controls kidney function in animals with established deoxycorticosterone acetate hypertension, the effects of acute renal surgical denervation were assessed in five normal and 10 deoxycorticosterone acetate-treated swine. After 12 to 16 weeks of treatment, mean arterial pressure rose from the normal level of 110 to 120 to 164 +/- 4 mm Hg but was decreased to 131 +/- 4 mm Hg by anesthesia. In the normal animals, blood pressure under anesthesia was 114 +/- 9 mm Hg. Acute left kidney surgical denervation significantly decreased renal vascular resistance and increased renal blood flow, glomerular filtration rate, urine flow, and sodium excretion only in the treated animals. In an additional group of six normal and eight deoxycorticosterone acetate-treated swine, the responses to renal pharmacological denervation with intrarenal guanethidine were evaluated. Guanethidine had no significant effect on renal blood flow, vascular resistance, glomerular filtration rate, urine flow, or sodium excretion in the normal animals. In contrast, in the mineralocorticoid-hypertensive animals, guanethidine significantly decreased renal vascular resistance and caused a diuresis and natriuresis with no change in glomerular filtration rate. We conclude that, in deoxycorticosterone acetate-treated miniature swine with established hypertension, renal nerve activity appears to be elevated and important in determining renal hemodynamics and sodium and water excretion.

The role of the sympathetic nervous system in 2-kidney DOCA-hypertensive Yucatan miniature swine.

To assess the mechanism responsible for maintaining the elevated arterial pressure in 2-kidney DOCA treated Yucatan miniature swine, cardiovascular parameters and the responses to hexamethonium bromide (HMB) were evaluated in normal and DOCA treated animals. Using chronically instrumented conscious animals, measurements of mean arterial pressure (MAP), cardiac output (CO), and calculated total peripheral resistance (TPR) revealed that with DOCA hypertension MAP was increased 50-60 mmHg above controls. This increased pressure was due to an increase in TPR with CO remaining normal. HMB normalized the MAP of the DOCA animals via a selective lowering of TPR to a value similar to that of the controls. In DOCA hypertensive animals these functional changes, due to increased peripheral sympathetic nerve activity, were reflected by significantly elevated plasma norepinephrine. In this animal DOCA administration produces a neurogenic form of hypertension which appears to be analogous to essential hypertension in man.

Baroreflex control of renal sympathetic nerve activity in hypertensive miniature swine.

The baroreceptor reflex control of renal nerve activity was examined in seven normotensive and 14 deoxycorticosterone acetate-treated anesthetized Yucatan miniature swine. Pressor responses evoked by the administration of phenylephrine were used to assess reflex control. The mean absolute threshold for inhibition of renal nerve activity was higher but not significantly different between the deoxycorticosterone acetate-treated and normotensive group. However, the mean relative threshold for inhibition of renal nerve activity was significantly greater in the deoxycorticosterone acetate-treated group (p less than 0.05). Responses from five deoxycorticosterone acetate-treated and five normotensive swine were used to examine the time course of the baroreflex inhibition of renal nerve activity. During the initial rise in pressure the percent inhibition of renal nerve activity was similar for the two groups. During the recovery phase of the response, renal nerve activity in the deoxycorticosterone acetate-treated group returned to baseline while renal nerve activity remained attenuated below baseline in the normotensive group. The gain of the reflex was significantly lower in the deoxycorticosterone acetate-treated group compared with the control group (p less than 0.05). The results of this study clearly indicate that baroreceptor reflex control of renal nerve activity is altered in anesthetized deoxycorticosterone acetate-treated hypertensive swine.