Showing papers by "Suzanne Oparil published in 1990"
TL;DR: Improved management is essential to avoid catastrophic injury to the central nervous system, the heart, and the kidneys as a result of a delay in initiating effective therapy or of overzealous therapy leading to a too-rapid reduction in blood pressure.
Abstract: OF the estimated 60 million Americans with hypertension, less than 1 percent will ever have a hypertensive crisis.1 The infrequency of such events can be attributed to improvements in the management of hypertension over the past 10 years. When patients do arrive at the emergency department or the physician's office with a critical elevation in blood pressure, proper management is essential to avoid catastrophic injury to the central nervous system, the heart, and the kidneys as a result of a delay in initiating effective therapy or of overzealous therapy leading to a too-rapid reduction in blood pressure. Hypertensive crisis is . . .
198 citations
TL;DR: The data suggest that a deficiency in circulating endogenous ANF may play a role in NaCI-sensitive hypertension in this model, and long-term infusion of exogenous ANF in a dose that resulted in plasma ANF levels well within the physiological range abolished the NaCl-induced exacerbation of hypertension in SHR-S.
Abstract: Our previous studies demonstrated that acute infusion of atrial natriuretic factor (ANF) produces an enhanced depressor response in NaCl-sensitive spontaneously hypertensive rats (SHR-S) fed a high (8%) NaCl diet compared with control SHR-S fed a normal (1%) NaCl diet and that dietary NaCl loading increases circulating ANF levels in Wistar-Kyoto (WKY) rats but not in SHR-S. The current study tested the hypotheses that 1) long-term infusion of ANF at a dose that elevates plasma ANF to levels comparable with those seen in high NaCl-fed WKY rats prevents the NaCl-induced exacerbation of hypertension in SHR-S and 2) ANF lowers blood pressure in this model by a sympatholytic effect. Male SHR-S received infusions of ANF (0.1 microgram/hr) or vehicle intravenously via osmotic minipump for 3 weeks beginning immediately before initiation of 1% or 8% NaCl diets at age 7 weeks. Chronic ANF infusion prevented the increase in arterial pressure in response to a high NaCl diet in SHR-S but had no effect in 1% NaCl-fed SHR-S. Thus, the NaCl-sensitive component of hypertension in SHR-S was more sensitive to ANF than the non-NaCl-sensitive component. Plasma norepinephrine was significantly increased in ANF-treated, 8% NaCl-fed SHR-S compared with vehicle controls, suggesting that ANF did not prevent NaCl-sensitive hypertension by a sympatholytic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
123 citations
TL;DR: The data demonstrate that chronic infusion of exogenous ANP at a dose that does not affect MPAP or RV weight in air-control rats attenuates the development of pulmonary hypertension and RV enlargement in rats adapted to chronic hypoxia.
Abstract: To test the hypothesis that chronic infusion of atrial natriuretic peptide (ANP) instituted before hypoxic exposure attenuates the development of pulmonary hypertension in hypoxia adapted rats, ANP (0.2 and 1.0 microgram/h) or vehicle was administered intravenously via osmotic minipump for 4 wk beginning before exposure to 10% O2 or to room air. Low dose ANP increased plasma ANP levels by only 60% of vehicle controls after 4 wk and significantly decreased mean pulmonary arterial pressure (MPAP) (P less than 0.01), the ratio of right ventricular weight to body weight (RV/BW) (P less than 0.01), and the wall thickness of small (50-100 microns) pulmonary arteries (P = 0.01) in hypoxia-adapted rats. ANP did not alter any of these parameters in air-control rats. High dose ANP increased plasma ANP levels by 230% of control and produced greater reductions in MPAP (P less than 0.001) and RV/BW) (P less than 0.05), but not in pulmonary arterial wall thickness, than the low dose. Neither dose of ANP altered mean systemic arterial pressure in either hypoxic or normoxic rats. The data demonstrate that chronic infusion of exogenous ANP at a dose that does not affect MPAP or RV weight in air-control rats attenuates the development of pulmonary hypertension and RV enlargement in rats adapted to chronic hypoxia.
67 citations
TL;DR: This trial clearly demonstrates that diltiazem SR and hydrochlorothiazide have additive antihypertensive effects and combination therapy was well tolerated.
Abstract: This multicenter, factorial-design trial assessed the safety and additive antihypertensive efficacy of a slow-release (SR) formulation of diltiazem hydrochloride given alone or in combination with hydrochlorothiazide for treatment of mild to moderate hypertension. After a 4- to 6-week placebo run-in period, 297 qualifying patients were randomized to receive placebo, 1 of 4 doses of diltiazem SR monotherapy, 1 of 3 doses of hydrochlorothiazide monotherapy, or 1 of 12 possible combinations of diltiazem SR and hydrochlorothiazide for 6 weeks. A dose-related reduction in blood pressure was demonstrated for each drug as monotherapy and for the two drugs in combination. Absolute blood pressures of patients who received combination therapy were lower by an overall mean of 3.0 mm Hg diastolic and 8.0 mm Hg systolic vs diltiazem SR used alone and 3.5 mm Hg diastolic and 4.0 mm Hg systolic vs hydrochlorothiazide used alone. At the largest doses used, 50% of patients achieved goal blood pressure while taking hydrochlorothiazide, 57% while taking diltiazem SR, and 75% while taking combination therapy. Combination therapy was well tolerated. This trial clearly demonstrates that diltiazem SR and hydrochlorothiazide have additive antihypertensive effects. (JAMA. 1990;263:1507-1512)
56 citations
TL;DR: The hypothesis that blockade of endogenous ANP in the anterior hypothalamus by local microinjection of a monoclonal antibody to ANP (MAb KY-ANP-II) lowers blood pressure in SHR-S is tested and it is shown that this region of brain known to influence cardiovascular function mediates BP and HR control in the rat.
Abstract: We have previously shown that the atrial natriuretic peptide (ANP) content of the anterior hypothalamic region of NaCl-sensitive spontaneously hypertensive rats (SHR-S) is higher than that of Wistar-Kyoto (WKY) rats. ANP has been shown to inhibit neuronal norepinephrine release and to reduce the excitability of hypothalamic neurons. This study tested the hypothesis that blockade of endogenous ANP in the anterior hypothalamus by local microinjection of a monoclonal antibody to ANP (MAb KY-ANP-II) lowers blood pressure in SHR-S. Purified MAb KY-ANP-II (0.055 and 0.55 micrograms) or control mouse IgG in 200 nl saline was microinjected into the anterior hypothalamic area (AHA) of conscious SHR-S and control WKY rats. As a further control, Mab KY-ANP-II (0.55 microgram) was microinjected into the posterior hypothalamic area (PHA) of SHR-S. Anterior hypothalamic microinjection of MAb KY-ANP-II caused significant dose-related decreases in mean arterial pressure (MAP) and heart rate (HR) in SHR-S but not in WKY rats. Control injections of equal volumes of IgG had no effect on MAP or HR. Microinjection of Mab KY-ANP-II into PHA produced no significant alteration in MAP or HR in SHR-S. These data provide the first demonstration that endogenous ANP in a region of brain known to influence cardiovascular function mediates BP and HR control in the rat. These findings suggest that the increased endogenous ANP in the anterior hypothalamus of SHR-S may be involved in the central regulation of BP in the model.
25 citations
TL;DR: Results indicate that alterations in CSF Na+ concentration do not contribute to the increase in arterial pressure induced by a high NaCl diet in SHR-S, and concomitant dietary Ca2+ supplementation attenuated the dietary NaCl-induced exacerbation of hypertension.
22 citations
TL;DR: The results suggest that the endogenous ANP may modulate pulmonary vascular tone in rats with hypoxic pulmonary hypertension.
Abstract: We demonstrated previously that intravenous administration of exogenous atrial natriuretic peptide (ANP) lowers mean pulmonary arterial pressure (MPAP) in hypoxia-adapted rats. To test the hypothesis that endogenous ANP may also lower MPAP in this model, C-ANP-(4-23), a ring-deleted analogue of ANP that binds to the biologically silent ANP clearance receptor (C-ANP receptor) but not to the ANP biological receptor (B-ANP receptor), was administered intravenously as a bolus injection (10 micrograms/kg) followed by an infusion (1 micrograms.kg-1.min-1 for 60 min) to rats adapted to hypoxia (10% O2) for 4 wk and to air control rats. C-ANP-(4-23) significantly lowered MPAP in hypoxic rats but not in air controls. A statistically insignificant reduction in mean systemic arterial pressure was found in both groups after C-ANP-(4-23) administration. C-ANP-(4-23) significantly (two- to threefold) increased endogenous plasma ANP levels in both groups; the increase was not significantly different between groups. Both basal and post-C-ANP-(4-23) levels of plasma ANP were greater in hypoxia-adapted animals than in air controls; the C-ANP-induced increase in plasma ANP was not significantly different between groups. These results suggest that the endogenous ANP may modulate pulmonary vascular tone in rats with hypoxic pulmonary hypertension.
19 citations
TL;DR: It is demonstrated that interleukin-2 was ineffective in preventing or attenuating hypertension in spontaneously hypertensive rats.
Abstract: It was recently reported that interleukin-2, when administered as a single bolus injection (5,000 units/kg), could prevent the development of hypertension in young spontaneously hypertensive rats and lower blood pressure to normotensive levels in spontaneously hypertensive rats with established hypertension. Consequently, efforts were made to duplicate this finding. Male spontaneously hypertensive rats (35 days old) were injected subcutaneously with 50,000 units/kg (3,500 units/rat) of recombinant interleukin-2 (Amgen) and had systolic blood pressure measured twice weekly by the tail-cuff technique. Systolic blood pressure in the interleukin-2-treated group was not significantly different from the vehicle-treated control group at any time point over 32 days of follow-up. A second injection of recombinant interleukin-2 (5,000 units/kg) was administered 32 days after the first injection. Again, no reduction in blood pressure was observed in the interleukin-2-treated group over an additional 38 days. Mean arterial pressure (+/- SEM) measured via intra-arterial cannula in conscious rats at age 105 days (38 days after the second treatment) was 168.5 +/- 3.5 mm Hg in interleukin-2-treated spontaneously hypertensive rats and 170.3 +/- 3.6 mm Hg in vehicle-treated controls. Both recombinant interleukin-2 preparations conformed to their respective manufacturer's indicated specific activity as determined by the ability of the interleukin-2 to induce proliferation of the interleukin-2-dependent cell line HT-2. Thus, this study demonstrated that interleukin-2 was ineffective in preventing or attenuating hypertension in spontaneously hypertensive rats.
15 citations
TL;DR: Dietary Ca2+ supplementation prevents the NaCl-induced exacerbation of hypertension and augmented depressor response to clonidine in SHR-S by increasing noradrenergic input to AHA, thereby preventing the upregulation of AHA alpha 2-adrenoceptors.
13 citations
8 citations
TL;DR: Dietary Ca2+ supplementation significantly increased the natriuretic and diuretic responses to saline infusion inSHR-S on the high NaCl diet, but not in SHR- S on the basal diet or in WKY on either diet.
Abstract: The present study tests the hypothesis that dietary Ca2+ supplementation increases acute diuretic and natriuretic responses to volume loading in the NaCl-sensitive spontaneously hypertensive rat (SHR-S). Seven week old male SHR-S and normotensive Wistar-Kyoto rats (WKY) were fed one of the following diets for 2.5 weeks: basal (0.75% NaCl, 0.68% Ca2+); high NaCl (8% NaCl, 0.68% Ca2+); high Ca2+ (0.75% NaCl, 2.0% Ca2+); and high NaCl and Ca2+ (8% NaCl, 2.0% Ca2+). SHR-S on high Ca2+ and on high NaCl and Ca2+ diets for 2 weeks displayed significantly lower systolic arterial pressures (SAP) than SHR-S on basal and high NaCl diets, respectively. WKY displayed no diet-related change in SAP at any time during the study. After 2.5 weeks on the diets, pre-instrumented, conscious SHR-S and WKY received an intravenous infusion (5% body weight) of isotonic NaCl, and urine was collected through a bladder catheter for a period of 90 min. The infusion did not alter the heart rate or the mean arterial pressure in any group. WKY on the high NaCl diet excreted a significantly greater percentage of the volume and Na+ load than WKY on the basal diet. In contrast, SHR-S on the high NaCl (compared to basal) diet did not display significantly enhanced natriuresis or diuresis. SHR-S on the basal diet displayed excretion rates similar to WKY on the basal diet. Dietary Ca2+ supplementation significantly increased the natriuretic and diuretic responses to saline infusion in SHR-S on the high NaCl diet, but not in SHR-S on the basal diet or in WKY on either diet.(ABSTRACT TRUNCATED AT 250 WORDS)
01 Jan 1990
TL;DR: The findings suggest that reduced noradrenergic input to sympathoinhibitory neurons in anterior hypothalamus contributes to NaCl-sensitive hypertension in spontaneously hypertensive rats.
Abstract: Previous studies from our laboratories demonstrated that dietary NaCl supplementation in NaCl-sensitive spontaneously hypertensive rats elevates blood pressure, increases peripheral sympathetic nervous system activity, and depresses endogenous norepinephrine stores and turnover in the anterior hypothalamus. These findings suggest that reduced noradrenergic input to sympathoinhibitory neurons in anterior hypothalamus contributes to NaCl-sensitive hypertension in spontaneously hypertensive rats. The current study tested the hypothesis that dietary NaCl supplementation depresses endogenous norepinephrine stores and turnover in anterior hypothalamus of two other NaCl-sensitive models of hypertension, the Dahl salt-sensitive rat and the deoxycorticosterone acetate/NaCl hypertensive rat, thus increasing blood pressure by reducing noradrenergic input to the anterior hypothalamus. Dahl salt-sensitive rats were fed a high (8%) NaCl diet, and deoxycorticosterone acetate/NaCl rats rats drank 1% NaCl solution ad libitum for 2 or 4 weeks. Age-matched Dahl salt-sensitive rats fed a basal 1% NaCl diet and uninephrectomized Sprague-Dawley rats drinking tap water were controls. Regional brain catecholamines were determined by high-performance liquid chromatography with electrochemical detection. Norepinephrine turnover in hypothalamus (anterior, posterior, and ventral regions) and brain stem (pons and medulla) was assessed using the dopamine beta-hydroxylase inhibitor 1-cyclohexyl-2-mercapto-imidazole. High NaCl treatment caused significant elevations in blood pressure in Dahl salt-sensitive and deoxycorticosterone acetate/NaCl rats, but endogenous norepinephrine levels and turnover rates were not significantly different in anterior hypothalamus or any other brain region studied between the NaCl-supplemented and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Because these measurements were obtained at trough, the data demonstrate that the antihypertensive activity of the diltiazem sustained-release and hydrochlorothiazide formulations lasts for at least 12 hours.
Abstract: In Reply.— We appreciate the opportunity to respond to the comments of Cappuccio et al. The measurement of blood pressure at 12 ± 2 hours after receiving a dose was not an SD but a commonly used protocol requirement that all blood pressure measurements be made within 12 ± 2 hours after dosing, and, in fact, 100% of the patients had these measurements at 10 to 14 hours after taking a dose, just before the next dose. Because these measurements were obtained at trough, the data demonstrate that the antihypertensive activity of the diltiazem sustained-release and hydrochlorothiazide formulations lasts for at least 12 hours. The diltiazem sustained-release preparation used in our study is the standard commercial preparation marketed in the United States (Cardizem SR, Marion Laboratories Inc, Kansas City, Mo). This product has been shown to have a consistent blood pressure—lowering effect throughout the dosing interval, with a duration of