Placenta growth factor is not an early marker for the development of severe preeclampsia.

OBJECTIVE: Our purpose was to determine whether plasma concentrations of placenta growth factor may be used as a marker for women who ultimately have severe preeclampsia. STUDY DESIGN: We performed a nested case-control study to compare plasma concentrations of placenta growth factor in women with severe preeclampsia with the concentrations in normotensive pregnant control subjects. Plasma samples were collected at <20 weeks' gestation and again in the third trimester. Twenty-two women who ultimately had severe preeclampsia were matched for gestational age at delivery with 22 normotensive control subjects. Placenta growth factor concentrations were measured by a specific antigen capture enzyme-linked immunosorbent assay. Comparisons were made by using the Mann-Whitney U test for nonparametric data such as placenta growth factor concentrations. The Student t test was used for parametric data. RESULTS: A total of 880 pregnant women were screened. Severe preeclampsia developed in 22, for an incidence of 2.5%. As expected, women with severe preeclampsia had significantly higher systolic and diastolic blood pressures, and their infants had lower birth weights. Placental weights at delivery were similar between those with severe preeclampsia and control subjects (659 vs 699 g; P =.51). During the third trimester, the median placenta growth factor concentrations were significantly lower in women with severe preeclampsia than in normotensive control subjects (125 vs 449 pg/mL; P =.003). When samples drawn at <20 weeks' gestation were compared, there was no difference between the group with severe preeclampsia and those who remained normotensive (98.8 vs 56.34 pg/mL; P =.15). CONCLUSION: During the third trimester, patients with severe preeclampsia have decreased maternal concentrations of placenta growth factor. This difference is not seen earlier in pregnancy. Lower concentrations of placenta growth factor may be a result of severe preeclampsia rather than a causal factor. Placenta growth factor is not a good marker for the subsequent development of severe preeclampsia.

Plasma, urinary, and salivary 8-epi-prostaglandin f2alpha levels in normotensive and preeclamptic pregnancies.

OBJECTIVE: Our purpose was to measure and compare plasma, urinary, and salivary concentrations of 8-epi-prostaglandin F(2alpha) (8-isoprostane) in women with normotensive pregnancies and the respective concentrations in pregnancies complicated by preeclampsia. STUDY DESIGN: Plasma, urinary, and salivary 8-isoprostane levels were measured in pregnant women with preeclampsia (n = 40), normotensive pregnant women (n = 20), and nonpregnant women (n = 10). One-way analysis of variance was used to determine significant differences. RESULTS: Plasma free 8-isoprostane concentrations were increased in women with severe preeclampsia (342 +/- 50 pg/mL), in comparison with nonpregnant women (129 +/- 17 pg/mL) and normotensive pregnant women (150 +/- 11 pg/mL; P =.003, and.0001, respectively). Urinary excretion of 8-isoprostane was slightly but not significantly decreased in preeclampsia (1200 +/- 227 pg/mL), in comparison with urinary excretion in nonpregnant women (1625 +/- 364 pg/mL) and normotensive pregnant women (2149 +/- 432 pg/mL). Salivary concentrations of 8-isoprostane were increased in normotensive women (496 +/- 113 pg/mL), in comparison with nonpregnant women (150 +/- 27 pg/mL) but were not related to preeclampsia (419 +/- 96 pg/mL; P

Evidence of a nonendothelial source of nitric oxide in the isolated perfused hindlimb vasculature of the pregnant rat.

OBJECTIVE: This study was undertaken to further elucidate the roles of the vascular endothelium and nitric oxide (NO) in the regulation of vascular tone and constrictor responsiveness in pregnancy. METHODS: The perfusion pressure-flow relationship was measured in isolated, perfused, norepinephrine-constricted (1) endothelium-intact, (2) endothelium-denuded, and (3) N omega-nitro-L-arginine methyl ester (L-NAME)-treated hindlimbs from nonpregnant and term-pregnant rates. RESULTS: Baseline perfusion pressure at a flow rate of 2 mL/min was similar (approximately 20 min Hg) in all hindlimbs. Norepinephrine (0.5 muM) increased perfusion pressure in both nonpregnant (+21.6 +/- 2.4 mm Hg) and pregnant (+13.6 +/- 0.9 mm Hg) endothelium-intact rat hindlimbs. In nonpregnant rat hindlimbs, endothelium removal and L-NAME increased norepinephrine vasoconstriction similarly (+44.3 +/- 4.0 mm Hg and +46.4 +/- 8.6 mm Hg, respectively). In pregnant-rat hindlimbs, L-NAME increased norepinephrine vasoconstriction by 43.5 +/- 10.8 mm Hg, similar to that in nonpregnant-rat hindlimbs, but endothelium removal only increased norepinephrine vasoconstriction by 28.0 +/- 2.2 mm Hg. Perfusion pressure increased linearly as the flow rate was increased from 2 to 4 mL/min, and the slope of the regression line of the endothelium-intact pregnant-rat hindlimbs (7.0 +/- 0.6) was slightly, but not significantly, lower than that of the nonpregnant-rat hindlimbs (9.6 +/- 0.9). Endothelium removal increased the slopes of the regression lines, but that of pregnant-rat hindlimbs (12.8 +/- 1.6) was significantly lower (p < or = 0.05) than that of the nonpregnant-rat hindlimbs (23.8 +/- 1.8). L-NAME caused a similar increase in the pressure-flow slopes of nonpregnant-rat (36.5 +/- 3.4) and pregnant-rat (32.1 +/- 5.3) hindlimbs. CONCLUSIONS: These results suggest that nonendothelial nitric oxide production may be increased in the hindlimb resistance vasculature of the pregnant rat, which may play a role in the normal pregnancy blunting of constrictor responsiveness and reduction of vascular resistance.

Effect of indomethacin and N omega-nitro-L-arginine methyl ester on the pressure/flow relation in isolated perfused hindlimbs from pregnant and nonpregnant rats.

OBJECTIVE: To compare the pressure/flow relationship and to assess the roles of prostaglandins and nitric oxide in flow-induced vasodilation in the nonpregnant and late-pregnant rat hindlimb vasculature. METHODS: Pressure/flow and conductance/flow relationships were determined in isolated, Krebs buffer-perfused, norepinephrine (0.5 mumol/L) preconstricted hindlimbs from nonpregnant and late-pregnant Wistar-Kyoto rats before and after inhibition of cyclo-oxygenase with indomethacin (20 mumol/L), or nitric oxide synthase with N omega-nitro-L-arginine methyl ester (300 mumol/L). RESULTS: There were no significant differences in baseline perfusion pressure between nonpregnant and pregnant rat hindlimbs perfused at 2 mL/min (20.6 +/- 0.8 and 19.7 +/- 1.1 mmHg, respectively) and norepinephrine increased perfusion pressure about twofold (40.8 +/- 2.0 and 34.8 +/- 1.8 mmHg, respectively). After constriction, perfusion pressure increased linearly as flow was increased in a stepwise manner to a maximum of 4 mL/min. The slope of the pressure/flow regression line for the pregnant rat hindlimbs (6.00) was significantly lower (P < or = .001) than that for the nonpregnant rat hindlimbs (8.44). Vascular conductance also increased as flow was increased, and was significantly greater at all flow rates in the pregnant compared to the nonpregnant rat hindlimbs. Indomethacin slightly decreased the constrictor response to norepinephrine and increased the pressure/flow regression line slope in nonpregnant, but not in pregnant rat hindlimbs. N omega-nitro-L-arginine methyl ester abolished flow-mediated vasodilation in nonpregnant and pregnant rat hindlimbs, and there was no longer any significant difference between the pressure/flow regression line slopes. CONCLUSION: These results suggest that flow-induced vasodilation, mediated by endothelium-derived nitric oxide, is enhanced during pregnancy allowing the maternal vasculature to accommodate increased blood flow without increased blood pressure.

The effect of chronic nitric oxide synthesis inhibition on blood pressure and angiotensin II responsiveness in the pregnant rat.

OBJECTIVES: Our purpose was to determine whether blockade of inducible or endothelial nitric oxide synthesis prevents maternal vasodilation and blunting of angiotensin II responsiveness in the pregnant rat. STUDY DESIGN: Pregnant and nonpregnant rats were given (1) drinking water alone (untreated), (2) drinking water containing the inducible nitric oxide synthase inhibitor aminoguanidine (0.5 gm/L), or (3) drinking water containing the nonselective nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (0.5 gm/L) from postmating days 5 to 21. On days 7, 14, and 20, 24-hour urinary nitrate-nitrite excretion, urine protein concentration, hematocrit, mean arterial blood pressure, and pressor responses to angiotensin II (12.5 to 200 ng/kg) were measured. On day 21 litter size, fetal weight, and fetal mortality were determined. RESULTS: Urinary nitrate-nitrite excretion was increased, and hematocrit and blood pressure were decreased by day 20 of pregnancy. Angiotensin II pressor responses were decreased on days 14 and 20 of pregnancy. Aminoguanidine slightly decreased nitrate-nitrite excretion in pregnant, but not nonpregnant rats, and abolished the late pregnancy increase. Aminoguanidine did not affect hematocrit, blood pressure, or angiotensin II responsiveness in either pregnant or nonpregnant rats. N omega-nitro-L-arginine methyl ester greatly reduced nitrate-nitrite excretion and induced hypertension in both nonpregnant and pregnant rats, but on day 20 blood pressure of the pregnant rats was significantly lower than that of the nonpregnant rats. N omega-nitro-L-arginine methyl ester increased angiotensin II responsiveness on days 14 and 20 only in the pregnant rats. N omega-nitro-L-arginine methyl ester, but not aminoguanidine, increased fetal mortality and decreased fetal weight. CONCLUSIONS: Inducible nitric oxide synthesis accounts for increased nitrate-nitrite excretion during pregnancy. Endothelium-derived nitric oxide may attenuate angiotensin II responsiveness but does not cause vasodilation and the fall in blood pressure during the last week of gestation.

Preeclampsia and related disorders. Clinical aspects and relevance of endothelin and nitric oxide.

Preeclampsia is a pregnancy-specific disorder believed to result from widespread endothelial dysfunction. Endothelin and NO are two potent vasoactive agents of endothelial origin and, as such, are postulated to play an important role in the pathogenesis of preeclampsia. If these agents are found to be important in preeclampsia, they will most likely exert their effects locally, rather than systemically. Future research on the autocrine and paracrine effects of endothelin and NO may yield important insights into the cause and pathogenesis of this enigmatic disease.

Magnesium sulfate therapy in preeclampsia is associated with increased urinary cyclic guanosine monophosphate excretion.

OBJECTIVE: Our objective was to determine if maternal urinary cyclic guanosine monophosphate levels are altered in preeclampsia. STUDY DESIGN: Aliquots from 24-hour urine samples collected from 57 women with preeclampsia and 14 normotensive pregnant women in the third trimester of pregnancy were assayed for urinary cyclic guanosine monophosphate. Urinary cyclic guanosine monophosphate values were expressed per milligram of urinary creatinine to standardize for renal function. RESULTS: There was no difference in gestational age at time of urine collection between the two groups. Urinary cyclic guanosine monophosphate levels (mean +/- SD) were similar between normotensive and preeclamptic pregnant women (751 +/- 498 vs 632 +/- 363 pmol/mg urinary creatinine, respectively, p = 0.12). Preeclamptic women receiving magnesium sulfate had significantly higher levels of urinary cyclic guanosine monophosphate than those not receiving magnesium sulfate (786 +/- 360 vs 555 +/- 344 pmol/mg urinary creatinine, respectively, p = 0.02). CONCLUSIONS: These preliminary results indicated that cyclic guanosine monophosphate excretion increases in patients with preeclampsia during magnesium sulfate infusion. The vascular smooth muscle relaxation effects of magnesium sulfate may be mediated by directly increasing cyclic guanosine monophosphate production or indirectly through endothelium-derived relaxing factor.

Endothelium-derived relaxing factor inhibition augments vascular angiotensin II reactivity in the pregnant rat hind limb.

OBJECTIVE: The purpose of our study was to determine whether endothelium-derived relaxing factor plays a role in the blunting of maternal vascular reactivity in pregnancy. STUDY DESIGN: We measured the concentration-pressor responses to norepinephrine (10(-8) to 10(-4) mol/L and angiotensin II (10(-10) to 10(-6) mol/L) in isolated, perfused hind limbs of nonpregnant and pregnant (postmating day 20 to 21) normotensive Wistar-Kyoto and spontaneously hypertensive rats. The hind limbs were perfused at 4 ml/min with Krebs-Ringer solution containing indomethacin (10(-5) mol/L to inhibit prostaglandin production and were either infused with N omega-monomethyl-L-arginine (10(-4) mol/L), a specific inhibitor of endothelium-derived relaxing factor synthesis, or 0.9% saline solution (untreated). RESULTS: Baseline perfusion pressure was similar in the nonpregnant and pregnant hind limbs of both strains, and N omega-monomethyl-L-arginine had no effect on perfusion pressure. Norepinephrine induced similar pressor responses in the nonpregnant and pregnant hind limbs of both strains, and N omega-monomethyl-L-arginine did not alter these responses. Angiotensin II pressor responses were significantly attenuated in the pregnant rat hind limbs compared with the nonpregnant rat hind limbs. N omega-monomethyl-L-arginine enhanced the angiotensin II responses in the pregnant, but not in the nonpregnant, rat hind limbs. CONCLUSION: The results suggest that rat pregnancy is not associated with generalized refractoriness to all vasoconstrictors and that endothelium-derived relaxing factor plays a role in attenuating vascular reactivity to angiotensin II.

Enhanced endothelium-derived relaxing factor activity in pregnant, spontaneously hypertensive rats.

Pregnancy is normally associated with vasodilation that, in hypertensive animals such as the spontaneously hypertensive rat, causes a profound decrease in blood pressure. To test the possibility that enhanced basal endothelium-derived relaxing factor activity has a role in the vasodilation of pregnancy, we measured the changes in mean arterial pressure and heart rate induced by NG-monomethyl-L-arginine, a specific inhibitor of endothelium-derived relaxing factor synthesis, in conscious nonpregnant and pregnant (postmating day 20 to 21) normotensive Wistar-Kyoto and spontaneously hypertensive rats. NG-monomethyl-L-arginine caused similar dose-dependent increases in mean arterial pressure in nonpregnant and pregnant Wistar-Kyoto rats, but the accompanying decrease in heart rate was significantly greater in nonpregnant rats than in pregnant ones. In the spontaneously hypertensive rats, NG-monomethyl-L-arginine caused significantly greater dose-dependent increases in mean arterial pressure in pregnant compared with nonpregnant rats; there were no differences in the decreases in heart rate. These pressor responses were partially reversed by excess L-arginine but not D-arginine. Indomethacin had no effect on the pressor response to NG-monomethyl-L-arginine or the depressor response to L-arginine after NG-monomethyl-L-arginine. Therefore basal endothelium-derived relaxing factor plays a role in vascular tone and blood pressure regulation in vivo, and pregnancy may be associated with enhanced basal endothelium-derived relaxing factor activity in the hypertensive spontaneously hypertensive rats.

Maternal and uteroplacental hemodynamic effects of chronic captopril in the hypertensive, term-pregnant rat.

The chronic effects of captopril on maternal hemodynamics and organ perfusion were investigated in 10 untreated and 10 captopril-treated pregnant spontaneously hypertensive rats by means of the radioactive-labeled microsphere technique. The normal decrease in blood pressure during gestation was prevented by reduction of litter size to two conceptuses on day 7 of gestation. Captopril (approximately 10 mg/kg/day) or drug vehicle (50% ethyl alcohol) was administered intraperitoneally by an osmotic pump from day 7 to 21. At term mean arterial pressure was 23% lower in the captopril-treated group as the result of a 29% decrease in total peripheral resistance without a significant change in cardiac output. The decrease in total peripheral resistance was primarily caused by a decline in splanchnic and skin resistances. Maternal organ and uteroplacental perfusion were not significantly altered. We conclude that administration of captopril during the last 2 weeks of pregnancy in the hypertensive rat effectively lowers maternal blood pressure without adverse effects on organ and uteroplacental perfusion.

The relationship between experimentally determined litter size and maternal blood pressure in spontaneously hypertensive rats.

Pregnancy lowers blood pressure in hypertensive rats. To evaluate the role of the conceptus in maternal blood pressure regulation, we measured the changes in systolic blood pressure b (by tail-cuff plethysmography) throughout gestation and mean arterial pressure, cardiac output, and organ blood flows (with radioactive microspheres) on postmating day 21 for calculation of total peripheral and organ vascular resistances in spontaneously hypertensive rats with litter size surgically adjusted to 0 to 10 conceptuses on postmating day 7. Blood pressure remained elevated in those rats with zero fetuses but decreased during the last week of pregnancy in those rats with three or more fetuses. The magnitude of the decrease was directly related to litter size. At term, cardiac output was positively correlated (r = 0.61; p less than 0.001), whereas mean arterial pressure and total peripheral resistance were negatively correlated (r = -0.74; p less than 0.001 and r = -0.79; p less than 0.001, respectively) with litter size. Resistances of all the vascular beds in the body, except the kidneys, spleen, and hepatic artery were also negatively correlated with fetal number. Thus pregnancy is characterized by a generalized maternal vasodilation, and the fetal/placental unit may play a significant role in modulating maternal vascular tone.

Lack of evidence of a vasodepressor role for relaxin in spontaneously hypertensive and normotensive pregnant rats.

To test the possibility that the ovarian polypeptide hormone relaxin mediates the vasodepressor effect of pregnancy, we measured changes in blood pressure in three groups of spontaneously hypertensive and Wistar-Kyoto normotensive rats: (1) pregnant, bilaterally oophorectomized rats on postmating day 13, (2) pregnant, sham-oophorectomized rats on postmating day 13, and (3) nonpregnant, sham-oophorectomized rats after 13 days. The day before parturition we also measured the pressor responsiveness to angiotensin II and norepinephrine. Systolic blood pressure fell significantly during the last week of gestation in both strains, reaching normotensive levels in the hypertensive rats by term. The pressor responsiveness to angiotensin II, but not norepinephrine, of the pregnant rats was reduced compared with that of the nonpregnant rats in both strains. Oophorectomy did not prevent the fall in blood pressure or the decrease in vascular reactivity to angiotensin II. Therefore, although ovarian relaxin secretion increases during pregnancy, it apparently does not decrease vascular sensitivity to angiotensin II or cause vasodilation.

Labetalol does not decrease placental perfusion in the hypertensive term-pregnant rat.

The acute effect of labetalol hydrochloride, a combined nonspecific beta-adrenergic and postsynaptic alpha 1-adrenergic blocker, on maternal hemodynamics and organ perfusion was investigated in 10 hypertensive, term-pregnant, spontaneously hypertensive rats with the use of the radioactive-labeled microsphere technique. The normal fall in blood pressure during pregnancy was prevented by the reduction of litter size to two conceptuses on day 7 of gestation. Labetalol (1 to 6 mg/kg) effectively lowered mean arterial pressure 22% by decreasing cardiac output 16%; total peripheral resistance was not significantly decreased. Thus, the blood pressure lowering effect of labetalol was due primarily to its beta-adrenergic blocking effect. Regional flows to the carcass and splanchnic circulation were decreased 19% and 15%, respectively, after labetalol administration. Uterine wall and ovarian perfusion were significantly reduced, but placental perfusion was not significantly altered. Because labetalol lowers blood pressure without reducing placental perfusion, it may be a useful alternative to hydralazine for the treatment of hypertensive emergencies in pregnancy.

Nifedipine does not adversely affect uteroplacental blood flow in the hypertensive term-pregnant rat.

The short-term effect of the calcium channel blocker, nifedipine, on maternal hemodynamics and organ perfusion was investigated in 12 hypertensive term-pregnant, spontaneously hypertensive rats by means of the radioactive-labeled microsphere technique. The normal fall in blood pressure during pregnancy was prevented by reducing litter size to two conceptuses on day 7 of gestation. Nifedipine (200 micrograms/kg) effectively lowered mean arterial pressure 25% by decreasing total peripheral resistance 38%. Cardiac output was increased 15%. Blood flows to the splanchnic region and the reproductive organs were increased after nifedipine administration. The increase in blood flow to the reproductive organs was the result of increased ovarian and uterine wall perfusion caused by large reductions in vascular resistances. Placental blood flow was not significantly altered, but resistance was decreased. Thus, the use of nifedipine to lower maternal blood pressure in pregnancy complicated by extreme hypertension does not necessarily decrease uteroplacental perfusion.

Polyriboinosinic:polyribocytidylic acid enhances rabbit slow-wave sleep.

Drowsiness and fever are common symptoms of many viral diseases. It has been postulated that double-stranded RNA (dsRNA) produced during viral replication may cause these symptoms by direct toxic effects or by inducing interferon (IFN) or other cytokine production. Polyriboinosinic:polyribocytidylic acid (poly I:C), a pyrogenic and IFN-inducing synthetic dsRNA, and polyriboadenylic:polyribouridylic acid (poly A:U), a less effective pyrogen and IFN-inducing substance, were used as models of viral dsRNA to further characterize the physiological response to dsRNA. Poly I:C was injected either intravenously or intracerebroventricularly into rabbits, and electroencephalograph, body movement, and brain temperature were monitored over the next 6 h; blood samples were taken 24 h postinjection. Poly I:C increased slow-wave sleep duration, suppressed rapid-eye-movement sleep, and induced fever but failed to raise plasma Cu. Dose-dependent responses occurred after intravenous or intracerebroventricular injections; minimal effective doses were 0.3 micrograms/kg (iv) and 1.0 ng (icv). Poly A:U failed to alter the sleep or temperature parameters measured. Responses elicited by poly I:C were distinct from those elicited by bacterial products, e.g., endotoxin enhances plasma Cu levels, thus implying different mechanisms. We conclude that poly I:C enhances slow-wave sleep and body temperature without provoking the acute-phase rise in plasma Cu. These effects may be initiated through an IFN-mediated process.

Effects of muramyl dipeptide on sleep, body temperature and plasma copper after intracerebral ventricular administration.

Muramyl peptides are the monomeric components of bacterial cell wall peptidoglycans. Many muramyl peptides, such as muramyl dipeptide (MDP), (N-acetylmuramyl-L-alanyl-D-isoglutamine), are immune response modifiers, pyrogenic and somnogenic. The purposes of this study were to measure the somnogenic effects of MDP in conjunction with a biochemical measure of the host defense response, plasma Cu, and to determine if plasma Cu levels, like sleep, are regulated by a central nervous system process. MDP administered into a lateral cerebral ventricle induced a dose-dependent rise in plasma copper at 28 h postinfusion. This was usually associated with dose-dependent fevers, increases in SWS and reductions in rapid eye movement (REM) sleep during the first 6 h after infusion. Intravenous (i.v.) administration of the same amount of MDP did not affect any of these variables. We conclude that the syndrome induced by centrally administered MDP includes activation of the host defense response with respect to a rise in plasma copper in addition to fever and enhanced sleep.

Thermal stimulation of the hypothalamus does not evoke the acute-phase reaction.

Interleukin-1 (IL1) injected into the preoptic-anterior hypothalamus (POAH) induces, besides fever, the hepatic synthesis of acute-phase glycoproteins. Since the febrigenic action of IL1 may involve thermosensitive neurons in the POAH, this study examined whether such neurons also might mediate the acute-phase response (APR). The POAH of six adult NZW rabbits was cooled (Tpo = 34.4 +/- 0.4 degrees C [mean +/- SD]) or heated (40.6 +/- 0.2 degrees C) continuously for 2.5 hr (so as to mimic the mean febrile course following a bolus microinjection of IL1 into the POAH). The ambient temperature (Ta) was 23.5 +/- 1.0 degrees C. Expectedly, core temperature fell and skin temperature rose on POAH heating, and the opposite occurred on POAH cooling. However, no statistically significant changes in the plasma levels of Fe, Zn, Cu, and N-acetylneuraminic acid, as indices of the APR, were induced by these treatments. These results indicate, therefore, that the central actions of IL1 in inducing fever and the APR are separate, and that the APR is not mediated through stimulation of thermosensitive units in the POAH.

Thermoregulatory responses of guinea pigs with anteroventral third ventricle lesions.

Guinea pigs with anteroventral third ventricle region (AV3V) lesions fail to develop fever and the associated rise in acute-phase plasma protein levels following systemic injections of lipopolysaccharide (LPS). Since endogenous pyrogen (EP) injected directly into the preoptic area of animals with AV3V lesions causes appropriate elevations in core temperature (Tco) and acute-phase plasma proteins levels, the blocked responses to LPS probably are not due to damage to the adjacent preoptic area. We proposed, therefore, that EP may pass from blood into brain in the AV3V, presumably through the organum vasculosum laminae terminalis. However, the possibility that a more generalized impairment due to damaged pathways within the AV3V could account for the observed effects was not examined. To investigate this possibility, guinea pigs were given AV3V lesions. Pending histological verification of the ablated sites, AV3V lesions were presumed to be placed correctly if the animals did not develop fever following LPS (Salmonella enteritidis, 2 micrograms/kg i.p., at ambient temperature (Ta) 22 degrees C); those failing to meet this criterion were designated as sham-operated. Two experiments were conducted. In the first, metabolic rates, Tco, and two skin temperatures (Tsk) were measured at Ta 12 degrees, 22 degrees, and 32 degrees C over an 8-month postlesion period during which failure to fever persisted; the data were collected during a 30-min period after thermal balance had been achieved at any given Ta. There were no differences in the variables measured between sham-operated and AV3V-lesioned animals at Ta 22 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Uteroplacental blood flow in the hypertensive, term pregnant, spontaneously hypertensive rat.

Carbohydrate overfeeding throughout pregnancy prevents the progressive fall in blood pressure to normotensive levels during the last week of gestation in the spontaneously hypertensive rat. Cardiac output, organ blood flows, and vascular resistances, measured with radioactive-labeled microspheres, were compared in three groups: carbohydrate-supplemented (hypertensive) term-pregnant rats, control-fed (normotensive) term-pregnant rats, and control-fed (hypertensive) nonpregnant rats. Blood pressure remained elevated in the carbohydrate-supplemented pregnant rats because the normal decrease in total peripheral resistance did not occur. There were no significant differences in organ blood flows between hypertensive and normotensive pregnant rats, with the exception of a 26% lower placental blood flow in the hypertensive versus the normotensive rats. Carbohydrate overfeeding was associated with reduced litter size but did not affect fetal growth. Both placental blood flow and litter size were inversely related to mean arterial blood pressure at term. This may be a useful model of essential hypertension during pregnancy.

The effect of hydralazine on placental perfusion in the spontaneously hypertensive rat.

Intravenous hydralazine was administered to 16 spontaneously hypertensive rats on day 21 of gestation. The radioactive labeled microsphere technique was used to assess the change in organ perfusion produced by the drug. Vascular resistance to most organs was decreased, except to the placentas, stomach, and cecum, where it increased by 43%, 104%, and 44%, respectively. Blood flow to the organs was redistributed, and although it was increased to the lungs, kidneys, liver, and adrenals, it was significantly reduced to the spleen, stomach, placentas, cecum, large intestine, and pancreas. The effect of hydralazine on placental perfusion was opposite to the effect on the uterus (myometrium). Patients with the highest blood pressures tend to have the poorest placental perfusion. Intravenous hydralazine should be used cautiously in these patients.