Showing papers by "Suzanne Oparil published in 1983"

Altered vascular reactivity and baroreflex sensitivity induced by chronic central administration of captopril in the spontaneously hypertensive rat.

Abstract: Previous studies from our laboratory have shown that chronic intracerebroventricular administration of captopril attenuates the development of hypertension in the spontaneously hypertensive rat of the Okamoto strain (SHR) without altering sodium and water balance, plasma renin, or sympathoadrenal activities. To determine whether the depressor effect of intracerebroventricular captopril was associated with an alteration in peripheral vascular reactivity and/or baroreflex sensitivity, vascular reactivity to phenylephrine and vasopressin was assessed in renal, mesenteric, and hindquarter vascular beds using pulsed Doppler flow probes. Captopril was infused into the jugular vein or lateral ventricle of male SHR and Wistar-Kyoto (WKY) rats for 4 weeks (osmotic mini pump, 1.25 micrograms/0.5 microliter/hr). Control SHR or WKY received intracerebroventricular infusions of vehicle. Four weeks of captopril decreased arterial pressure in both SHR and WKY. In response to phenylephrine and vasopressin, SHR and WKY treated with intracerebroventricular captopril showed significantly attenuated increases in arterial pressure and vascular resistance in comparison to either vehicle-treated rats or rats receiving intravenous captopril. Reflex decreases in heart rate in response to phenylephrine were also greater in SHR and WKY treated with intracerebroventricular captopril than in the other rat groups. Neither vascular reactivity nor baroreflex sensitivity was altered in rats treated with intravenous captopril. We conclude that the depressor effect of captopril involves a blunting of vascular reactivity to vasoconstrictors and a potentiation of the baroreflex.

Attenuation of the development of spontaneous hypertension in rats by chronic central administration of captopril.

Abstract: Captopril infused into the lateral ventricle (ICV) of adult spontaneously hypertensive rats (SHR) decreases blood pressure. The current study was designed to explore the effects of brain converting-enzyme inhibition in young animals before the development of established hypertension and to characterize changes induced by captopril in a variety of pressor systems that might be responsible for the development of hypertension in this strain. Captopril (1.25 micrograms/0.5 microliter/hr) was infused into male SHR starting at 7 weeks of age. Four weeks later systolic blood pressure was only 157 +/- 3.3 compared to 181 +/- 3.9 mm Hg in vehicle-infused controls, and the pressor effect of ICV-injected angiotensin I was attenuated by 50%. When the same dose of captopril was infused intravenously, hypertension progressed as in vehicle-treated rats. Serum angiotensin-converting enzyme activity (SACE) and plasma arginine vasopressin (AVP) concentration were significantly higher (p less than 0.001 and 0.05, respectively), in the ICV captopril group than in the ICV vehicle group, while plasma aldosterone concentration and renin activity, fluid intake, urine volume, and urinary sodium excretion were similar in the two groups. Peripheral sympathetic nervous system activity assessed in the resting state was not altered by captopril treatment. In addition, AVP content of the telencephalon, diencephalon, mesencephalon, and pons medulla were not altered by ICV captopril. Renin activity was elevated in the telencephalon of ICV captopril-treated animals but unaltered in the other brain regions examined. These data demonstrate that ICV administration of captopril attenuates the development of hypertension in young SHR by mechanisms apparently independent of altered fluid and sodium balance and the sympathoadrenal system. The effect on blood pressure occurs in the absence of changes in renin activity or AVP content of plasma or those brain regions most often associated with blood pressure control.

Role of the renal nerves in the maintenance of DOCA-salt hypertension in the rat. Influence on the renal vasculature and sodium excretion.

Abstract: We previously observed that the renal nerves facilitate sodium retention and contribute to the development of DOCA-salt hypertension in the rat. To determine whether the renal nerves also participate in the maintenance of DOCA-salt hypertension, we studied the effects of renal denervation after 3 or 10 weeks of DOCA-salt treatment on systolic blood pressure, urinary sodium excretion, creatinine clearance, and precapillary arteriolar wall/lumen ratios of renal, hindlimb muscle, and cremaster muscle vascular beds. Systolic blood pressures of animals given DOCA-salt reached a plateau by 3 weeks of treatment at which time a sham operation or renal denervation was performed. Sham operation in hypertensive animals resulted in no change in systolic blood pressure and no change in percent sodium intake excreted. Wall/lumen ratio of the renal precapillary arteriole in sham-operated hypertensive animals was increased compared to similar sized vessels in hindlimb and cremaster muscle. In contrast, renal denervation resulted in a natriuresis and an attenuation of the hypertension (208 +/- 7 mmHg; p less than 0.01). Wall/lumen ratio of the renal capillary arterioles in renal denervated animals was no different than similar sized vessels in hindlimb and cremaster muscle and significantly less than that seen in sham-operated animals (0.85 +/- 0.05 vs 1.03 +/- 0.06; p less than 0.05). In another group of animals, sham operation or renal denervation was performed after 10 weeks of DOCA-salt treatment. At this time neither operation altered systolic blood pressure or sodium balance. In contrast to 3-week DOCA-salt-treated hypertensive sham-operated animals, renal precapillary arteriolar wall/lumen ratio of 10-week animals was no different than similar sized vessels in hindlimb and cremaster muscle. In addition, renal precapillary arteriolar wall/lumen ratio of 10-week DOCA-salt-treated renal-denervated animals was no different than that seen in 10-week DOCA-salt-treated sham-operated hypertensive animals. Creatinine clearance of the 10-week DOCA-salt-treated sham-operated or renal-denervated animals was significantly (p less than 0.01) lower than that of the 3-week DOCA-salt-treated groups (0.25 +/- 0.14 vs 1.03 +/- 0.10 ml/min). These data suggest that the renal nerves contribute to the early established phase of DOCA-salt hypertension by shifting the arterial pressure-renal sodium excretion curve to the right. With time, the renal nerves play a diminishing role in the maintenance of established DOCA-salt hypertension in the rat, while other renal factors, including decreased glomerular filtration rate and probable fixed renal vascular changes, play an increasingly important role.

Kidney function and sodium handling in the pregnant spontaneously hypertensive rat.

Abstract: Effects of gestation on volume homeostasis and renal function were studied in awake spontaneously hypertensive rats (SHR). Systolic blood pressure was similar to that of virgin littermates during most of SHR pregnancy but decreased near term (p less than 0.005). Plasma renin activity was lower in SHR than in age-matched Wistar-Kyoto (WKY) rats (p less than 0.001), but values were similar in gravid and nonpregnant animals from each strain. Renal renin content and lipid volume fractions of papillary interstitial granules were significantly greater in pregnant animal of each strain and those of the gravid WKY were also greater than both pregnant and virgin SHR. Saralasin had no effect on mean arterial pressure in gravid and virgin rats from either group. Plasma volume increased significantly near term in animals of both strains. Kidney weight, glomerular filtration rate (GFR), and renal blood flow were lower in SHR compared to WKY, and the hypertensive rats failed to demonstrate an increase in GFR during gestation, unlike the WKY. All SHR and pregnant WKY excreted infused sodium better than the virgin WKY. Also, regular Wistar animals excreted a salt load better than the virgin WKY. Finally, uterine blood flow, pup number and conceptus weight were similar in SHR and WKY. We conclude that pregnancy induces a decrease in blood pressure in SHR, and that angiotensin II does not seem to play an important role in maintaining blood pressure during gestation in either SHR or WKY. Despite a lower GFR and its failure to increase during pregnancy, renal sodium handling is not impaired in the SHR. The virgin WKY has a decreased ability to excrete sodium which is ameliorated during gestation.

Intrarenal angiotensin I conversion at normal and reduced renal blood flow in the dog.

Abstract: Intrarenal conversion of angiotensin I (ANG I) to angiotensin II (ANG II) under conditions of normal and reduced renal blood flow (RBF) elicited by constriction of the renal artery was examined in pentobarbital-anesthetized dogs. In eight animals, tracer doses of 125I-ANG I (5-12 pmol) were injected into the renal artery and 125I-ANG I, 125I-ANG II, and 125I-labeled metabolites were measured in renal venous effluent by high-voltage paper electrophoresis. The mean conversion of ANG I to ANG II during a single passage through the kidney was 21.8 +/- 2.1% at control RBF. When RBF was decreased by 25 and 53%, percent ANG I conversion was not altered significantly. In six dogs percent conversion of 125I-[Sar1, Ile5]ANG I, an ANG I analogue refractory to hydrolysis by aminopeptidases, was 18.1 +/- 1.7% at control RBF and did not change significantly when the RBF was reduced by 55%. Although there were severalfold increases in renal renin secretion rate and net ANG I generation rate during reduced RBF, net renal ANG II formation rate did not change significantly. These data indicate that there is substantial conversion of ANG I in a single passage through the dog kidney and that intrarenal ANG I conversion is independent of RBF even under conditions in which renin secretion rate and ANG I generation rate are increased severalfold.

Central catecholamine depletion, vasopressin, and blood pressure in the DOCA/NaCl rat.

Abstract: To determine whether impaired arginine vasopressin (AVP) release occurs when DOCA-NaCl hypertension is prevented following chemical sympathectomy with 6-hydroxydopamine (6-OHDA), male Sprague-Dawley rats treated with intraventricular injections of 6-OHDA (250 micrograms X 2) or Merlis solution received deoxycorticosterone acetate (DOCA) implants (100 mg/kg) and drank 0.5% saline. Systolic blood pressure in the 6-OHDA-treated DOCA/NaCl group (139 +/- 4 mmHg) was lower (P less than 0.001) than in the Merlis-DOCA/NaCl group (183 +/- 7 mmHg). 6-OHDA treatment produced widespread catecholamine depletion throughout the central nervous system, including the supraoptic and paraventricular nuclei, the cells of which are known to produce AVP, but hypothalamic, pituitary, and plasma AVP levels were similar in both experimental groups, the latter values averaging 1.5-2 times those of controls. Both groups of rats suppressed AVP secretion appropriately when water loaded. Such suppression, however, had no effect on blood pressure in the hypertensive animals and, furthermore, administration of the AVP antagonist d(CH2)5Tyr(Me)AVP produced small decrements in mean blood pressure of both groups that were not significantly different from responses seen in control normotensive rats. These data demonstrate that 6-OHDA does not prevent DOCA-NaCl hypertension by decreasing AVP levels and suggest that AVP is not necessary for the maintenance of hypertension in this model.