Abstract-The purpose of this study was to examine the role of the renin-angiotensin system in mediating the hypertension in response to chronic reductions in uterine perfusion pressure (RUPP) in conscious chronically instrumented pregnant rats. Mean arterial pressure was significantly higher in pregnant rats with chronic RUPP (125Ϯ3.0 mm Hg, PϽ0.01, nϭ12) than in pregnant rats (100Ϯ2.3 mm Hg, nϭ17). Plasma renin activity in pregnant rats with chronic RUPP was 17.1Ϯ2.5 nmol angiotensin I · L Ϫ1 · h Ϫ1 compared with 21.9Ϯ3.5 nmol angiotensin I · L Ϫ1 · h Ϫ1 in pregnant rats. Chronic oral administration of a converting-enzyme inhibitor (enalapril, 250 mg/L for 6 days) decreased mean arterial pressure to a similar extent in pregnant rats with chronic RUPP (109Ϯ4.2 mm Hg, PϽ0.01, nϭ9) and in normal pregnant (81Ϯ1.8 mm Hg, PϽ0.01, nϭ9) rats. Blockade of the renin-angiotensin system, however, had no significant effect on the blood pressure response to chronic RUPP as differences were similar in control (⌬25 mm Hg) and convertingenzyme inhibitor-treated (⌬27 mm Hg) groups. These findings suggest that the renin-angiotensin system does not play a major role in mediating the hypertension produced by chronic RUPP in pregnant rats. Key Words: hypertension, pregnancy Ⅲ preeclampsia Ⅲ renin-angiotensin system Ⅲ enalapril Ⅲ blood pressure A leading theory concerning the pathophysiology of preeclampsia suggests that a pathway that starts with inadequate trophoblast invasion of maternal spiral arteries leads to decreased placental perfusion. The ensuing placental ischemia results in placental release of factors, subsequent maternal endothelial dysfunction, and systemic vasoconstriction. 1,2 A variety of animal models have shown that a reduction in uterine perfusion pressure (RUPP) leads to systemic hypertension in pregnant animals [3][4][5][6] ; however, the mechanisms involved in mediating this hypertensive response to RUPP are unknown.The renin-angiotensin system (RAS) plays an important role in the long-term regulation of renal function and arterial pressure during a variety of both physiological and pathophysiological conditions. 7 During normal pregnancy, the RAS is thought to respond to hormonal changes and contribute to maintenance of blood pressure, blood flow, and sodium balance. 8 Activation of RAS during pregnancy is evident by the marked changes that occur in the RAS as plasma renin activity (PRA), plasma renin concentration, angiotensinogen, and angiotensin (Ang) II levels are all elevated, whereas vascular responsiveness to Ang II appears to be reduced. 8,9 In women with preeclampsia, these same components of the RAS are altered as PRA, plasma renin concentration, angiotensinogen, plasma aldosterone, and plasma Ang II are reduced, whereas sensitivity to Ang II is increased compared with that of normotensive pregnant women. 8,9 Therefore, significant changes are observed in the RAS in preeclamptic pregnancy compared with normal pregnancy.A role for the RAS in both human preeclampsia and in mediating pregnancy-induced...

Abstract-Acute, nonselective nitric oxide synthase inhibition in the pregnant rat decreases glomerular filtration rate and renal plasma flow, suggesting a role for nitric oxide in mediating renal vasodilation during pregnancy. As mid-gestation in the rat is associated with a significant increase in renal protein expression of inducible nitric oxide synthase, the aim of this study was to examine the role of inducible nitric oxide synthase in mediating renal hemodynamics changes at mid-gestation in the rat. At day 16 of pregnancy, glomerular filtration rate was significantly higher in pregnant rats compared with virgin rats (3.1Ϯ0.4 versus 2.7Ϯ0.3 mL/min, respectively; PϽ0.05), as was effective renal plasma flow (13.4Ϯ2.5 versus 10.9Ϯ2.2 mL/min, respectively; PϽ0.05). Acute administration of the inducible nitric oxide synthase selective inhibitor, AMT hydrochloride (750 nmol/h), markedly attenuated the increase in glomerular filtration rate observed in pregnant rats (2.3Ϯ0.2 mL/min, PϽ0.01 versus pregnant) without significantly altering glomerular filtration rate in virgin rats (2.1Ϯ0.2 mL/min). Acute AMT administration significantly decreased effective renal plasma flow in pregnant (8.9Ϯ1.8 mL/min, PϽ0.01 versus pregnant) and virgin rats (7.1Ϯ0.9 mL/min, PϽ0.05 versus virgin). Acute administration of EIT (380 nmol/h), another inducible nitric oxide synthase selective inhibitor, also attenuated pregnancy-induced increases in glomerular filtration rate (2.1Ϯ0.2, 2.8Ϯ0.3, and 2.3Ϯ0.3 mL/min; virgin, pregnant, and EIT, respectively) and effective renal plasma flow (8.5Ϯ1.1, 13.8Ϯ2.1, and 9.0Ϯ1.1 mL/min; virgin, pregnant, and EIT, respectively). Therefore, these findings suggest that inducible nitric oxide synthase may play an important role in mediating the renal hemodynamic changes that occur during normal pregnancy. Key Words: pregnancy Ⅲ nitric oxide synthase Ⅲ kidney Ⅲ hemodynamics Ⅲ rats N ormal pregnancy is associated with significant increases in renal hemodynamics as increases in glomerular filtration rate (GFR) and renal plasma flow (RPF) of Ͼ40% are observed in pregnant women. 1 In the rat, GFR and RPF are increased by Ͼ20% at mid-gestation with a return to prepregnant values by late pregnancy. 2,3 These increases in renal hemodynamics at mid-gestation in the rat are associated with significant increases in whole-body nitric oxide (NO) production 3,4 and renal protein expression of both inducible and neuronal nitric oxide synthase (iNOS and nNOS, respectively). 3 A role for NO in mediating renal vasodilation during pregnancy is suggested in a study by Danielson and Conrad in which acute nonselective NOS inhibition equalized GFR and effective RPF (ERPF) in virgin rats and pregnant rats at mid-gestation. 5 However, nonselective inhibition of all three NOS isoforms, endothelial (eNOS), neuronal (nNOS), and inducible (iNOS), does not elucidate which specific isoform is an important source of NO during pregnancy.Several lines of evidence suggest that NO generated by the iNOS isoform may play an important role in...