Showing papers by "Suzanne Oparil published in 1997"

Angiotensin II formation from ACE and chymase in human and animal hearts: methods and species considerations.

Abstract: The current study examined the contributions of angiotensin-converting enzyme (ACE) vs. chymase to angiotensin II (ANG II) generation in membrane preparations from left ventricles of humans, dogs, ...

Compartmentalization of angiotensin ii generation in the dog heart : evidence for independent mechanisms in intravascular and interstitial spaces

Abstract: Angiotensin-converting enzyme inhibitors have beneficial effects that are presumably mediated by decreased angiotensin II (ANG II) production. In this study, we measure for the first time ANG I and ANG II levels in the interstitial fluid (ISF) space of the heart. ISF and aortic plasma ANG I and II levels were obtained at baseline, during intravenous infusion of ANG I (5 microM, 0.1 ml/min, 60 min), and during ANG I + the angiotensin-converting enzyme inhibitor captopril (cap) (2.5 mM, 0.1 ml/min, 60 min) in six anesthetized open-chested dogs. ISF samples were obtained using microdialysis probes inserted into the left ventricular myocardium (3-4 probes/dog). ANG I increased mean arterial pressure from 102+/-3 (SEM) to 124+/-3 mmHg (P 100-fold higher than plasma levels, and did not change from baseline (8,122+/-528 and 6,333+/-677), during ANG I (8,269+/-502 and 6, 139+/-695) or ANG I + cap (8,753+/-502 and 5,884+/-695). The finding of very high ANG I and ANG II levels in the ISF vs. intravascular space that are not affected by IV ANG I or cap suggests that ANG II production and/or degradation in the heart is compartmentalized and mediated by different enzymatic mechanisms in the interstitial and intravascular spaces.

The orally active nonpeptide endothelin A-receptor antagonist A-127722 prevents and reverses hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling in Sprague-Dawley rats.

Abstract: Exposure to hypoxia is associated with increased pulmonary artery pressure and plasma endothelin (ET-1) levels and with selective enhancement of ET-1 peptide and messenger RNA (mRNA) and endothelin-A (ET-A) receptor mRNA in rat lung. Our study tested the hypothesis that A-127722, an orally active antagonist of the ET-A receptor, can prevent hypoxia-induced pulmonary hypertension and vascular remodeling in the rat. Pretreatment with A-127722 (3, 10, and 30 mg/kg/day in drinking water for 2 days) caused dose-dependent inhibition of the pulmonary vasoconstrictor response to short-term hypoxia (10% O2, 90 min). Long-term A-127722 treatment (10 mg/kg/day in drinking water for 2 weeks) instituted 48 h before hypoxic exposure attenuated the subsequent development of pulmonary hypertension, the associated right atrial hypertrophy, and pulmonary vascular remodeling. Institution of A-127722 treatment (10 mg/kg/day in drinking water for 4 weeks) after 2 weeks of hypoxia retarded the progression of established hypoxia-induced pulmonary hypertension and right atrial hypertrophy and reversed the pulmonary vascular remodeling despite continuing hypoxic exposure. These findings support the hypothesis that endogenous ET-1 plays a major role in hypoxic pulmonary vasoconstriction/hypertension, right heart hypertrophy, and pulmonary vascular remodeling and suggest that ET-A receptor blockers may be useful in the treatment and prevention of hypoxic pulmonary hypertension in humans.

Nutritional management of cardiovascular risk factors. A randomized clinical trial.

Abstract: Background: Adherence to dietary recommendations for disease management is often hindered by the complexity of incorporating them into the daily diet. Nutrition and cardiovascular scientists and food technologists collaborated to develop a prepared meal plan that meets national dietary guidelines for cardiovascular risk reduction. Objective: To assess the clinical effects of this plan, which incorporates all National Academy of Sciences National Research Council recommended dietary allowances for vitamins, minerals, and macronutrients, compared with a patient-selected American Heart Association Step I and Step II diet plan. Methods: This multicenter, randomized, parallel-intervention trial was conducted at 10 medical centers in the United States and Canada and involved 560 men and women with hypertension, dyslipidemia, or diabetes. Following calculation of prescriptions to meet individual nutritional requirements based on the HarrisBenedict equation, participants were randomized to the Campbell's Center for Nutrition and Wellness (CCNW) plan, which is composed of prepackaged breakfast, lunch, and dinner meals provided to participants, or a nutritionist-guided American Heart Association Step I and Step II diet, in which participants self-selected foods to meet their nutrition prescription for 10 weeks. Main Outcome Measures: Blood pressure (BP); lipid, glucose, glycosylated hemoglobin (HbA1c), and insulin levels; body weight; dietary intake; and quality of life. Results: Patients' BP, lipid levels, carbohydrate metabolism, weight, and quality of life (P≤.001 for all findings except low-density lipoprotein-high-density lipoprotein ratio,P=.25) all improved on both nutrition plans. Mean differences (±SD) between baseline and treatment clinical values for the CCNW and the self-selected diet groups (between-groupPvalues), respectively, were as follows: systolic BP, -6.4±9.2 mm Hg and -4.6±9.0 mm Hg (P=.02);ic BP, -4.2±5.7-4.2±5.7 -3.0±5.1 m-3.0±5.1 mm Hg (P=.006)rol, -0.32±0.58-0.32±0.58 mmol/L and -0.27±0.56 mmol/L(-12.4±22.5 mg/dL and -10.4±21.9 mg/dL) (P=.30); glucose, -0.65±1.88 mmol/L andm-0.75±2.03 mmol/L (-11.7±34.0 mg/dL and -13.5±36.6 mg/dL) (P=.10); and HbA1c, -0.4%±0.8% and -0.3%±0.7% (P=.66). Weight loss with the CCNW and self-selected plans, respectively, was as follows: men, -4.5±3.6 kg and -3.5±3.3 kg; and women, -4.8±3.0 kg and -2.8±2.8 kg. Quality of life was significantly improved for daily and work activities (P Conclusions: Nutritionally balanced meals that meet the recommendations of national health organizations improved multiple risk factors for patients with cardiovascular disease. The CCNW plan resulted in greater clinical benefits, nutritional completeness, and compliance than the self-selected diet. The CCNW is a comprehensive nutrition plan, convenient for both prescription and practice, and appears viable for effecting favorable dietary changes in patients at high risk for cardiovascular disease. disease. Arch Intern Med. 1997;157:169-177

Sexually dimorphic response of the balloon-injured rat carotid artery to hormone treatment.

Abstract: Background Estrogen blunts the neointimal response to vascular injury in gonadectomized rats of both sexes; addition of a progestin blocks the estrogen effect. This study tested, in intact rats of both sexes, whether (1) exogenous estrogen has a vasoprotective effect in injured carotid arteries, (2) progestin (medroxyprogesterone acetate, MPA) blocks the vasoprotective effect of estrogen, and (3) any observed sexual dimorphism in the responses to estrogen and/or MPA can be accounted for by differences in serum 17β-estradiol levels. Methods and Results Intact male and female Sprague-Dawley rats were randomly divided into four subgroups treated with either (1) 17β-estradiol, (2) MPA, (3) 17β-estradiol+MPA, or (4) vehicle and were subjected to balloon injury of the right common carotid artery. Two weeks later, rats were killed by an overdose of pentobarbital, and the carotid arteries were evaluated for myointimal thickening. Neither estradiol nor MPA altered the neointimal response in males. In females, estr...

Estrogen Restores Endothelial Cell Function in an Experimental Model of Vascular Injury

Abstract: Background It has been suggested that reendothelialization of damaged blood vessels protects against the vascular injury response. The goal of the present study was to determine whether estrogen restores endothelial cell function in balloon-injured rat carotid arteries. Methods and Results Ten-week-old male and female Sprague-Dawley rats with intact gonads underwent balloon injury to the right common carotid artery. Female rats were randomized to receive either daily subcutaneous injections of 17β-estradiol (17β-E2; 20 μg · kg−1 · d−1) or vehicle over the course of the study. Vessel morphology was assessed 2 weeks after injury. Significant neointima formation was observed in vehicle-treated males. This response was blunted in vehicle-treated and 17β-E2–supplemented females. Intima-to-media ratios were 1.28±0.23 (males), 0.72±0.07 (vehicle-treated females), and 0.49±0.07 (17β-E2–supplemented females). To test whether reductions in neointimal lesion formation were related to the functional reendothelializat...

Hypoxia stimulates human preproendothelin-1 promoter activity in transgenic mice

Abstract: Significant elevations in endothelin (ET)-1 levels accompany many diseases, but the underlying regulatory mechanisms are unclear. To investigate the in vivo regulation of human preproendothelin-1 (...

Scientists’ statement regarding data on the sodium-hypertension relationship and sodium health claims on food labeling

Abstract: Nutrition Reviews has had a continuing interest in the scientific basis of arguments for and against health claims on foods. Such claims were first authorized by the Food and Drug Administration (FDA) in 1993 under the terms of the Nutrition Labelling and Education Act of the U.S. Congress, passed in 1990. Since then there have been petitions that have resulted in a newly authorized claim for oats and other petitions directed toward modification or deletion of the originally approved claims. The Salt Institute, an industry-supported organization, has actively participated in the discussions regarding the sodium and hypertension health claim. The scientists signing this statement are familiar with the evolving understanding of the relationship between sodium and hypertension. The statement reviews more recent studies and critiques the arguments for a sodium health claim. We invite our readers to respond to the discussion in this controversial area of nutrition science and policy.

High blood pressure in women.

Abstract: There is a sexual dimorphism in blood pressure of humans and experimental animals: males tend to have higher blood pressure than females with functional ovaries, while ovariectomy or menopause tends to abolish the sexual dimorphism and cause females to develop a "male" pattern of blood pressure. Hypertensive male laboratory animals tend to have NaCl-sensitive blood pressure, while females are NaCl resistant unless their ovaries are removed, in which case NaCl sensitivity appears. The hormonal basis of NaCl sensitivity of blood pressure and of the sexual dimorphism of hypertension remains to be defined. Synthetic estrogens and progestins, as found in oral contraceptives, tend to elevate blood pressure, while naturally occurring estrogens lower it, or have no effect. Hypertension increases cardiovascular risk in women, as well as men, although the benefits of antihypertensive treatment have been more difficult to demonstrate in women. In the population of the United States, women are more aware of their hypertension, more likely to be treated medically, and more likely to have their blood pressure controlled.

Antihypertensive effects of mibefradil in the treatment of mild-to-moderate systemic hypertension.

Abstract: This report summarizes the results of 4 double-blind, placebo-controlled studies designed to determine the efficacy, tolerability, and dose-response characteristics of the novel T-channel-selective calcium antagonist, mibefradil, in the treatment of mild-to-moderate essential hypertension. Two of these studies were conducted in the general population of essential hypertensives, 1 in elderly patients, and 1 in patients on chronic hydrochlorothiazide treatment. A total of 1,116 patients were randomized to receive 1 of 7 doses of mibefradil (6.25–200 mg; n = 927), or placebo (n = 189). Each study demonstrated a significant linear dose response in the reduction of sitting diastolic (SDBP) and sitting systolic (SSBP) blood pressure. In all 4 trials, SDBP was significantly reduced with the recommended doses of 50 and 100 mg mibefradil (placebo-corrected treatment effects of −4.1 to −6.8 mm Hg and −8.8 to −11.1 mm Hg, respectively, for the 50- and 100-mg doses). A similar reduction in SSBP occurred in 3 of 4 studies at the 50-mg dose (−7.5 to −10.7 mm Hg) and in 4 of 4 studies at the 100-mg dose (−6.8 to −16.7 mm Hg). Lower doses did not reduce blood pressure significantly; doses >100 mg had little additional effect and an increased incidence of adverse events. Overall, response and normalization rates were dose related and averaged 61% and 51%, respectively, for the 50-mg dose and 78% and 65%, respectively, for the 100-mg dose. The onset of the antihypertensive effect was gradual, with no first-dose effect; near maximal response was reached within 1–2 weeks. Trough/peak ratios ranged from 77–86% with the 50-mg dose and from 77–108% with the 100-mg dose, indicating a sustained effect over a 24-hour period. A slight decrease in heart rate was observed, ranging from −2.2 to −5.5 beats/min at the 50-mg dose and from −4.0 to −8.8 beats/min at the 100-mg dose. The efficacy and safety results were similar across all populations studied, including the elderly and hydrochlorothiazide-treated patients, indicating that no dose adjustment is needed for these populations. Thus, the results of these 4 placebo-controlled trials confirm that when taken at the recommended doses of 50 and 100 mg once daily, mibefradil is an effective, safe, and well-tolerated therapy for the treatment of mild-to-moderate hypertension.

Tolerability profile of tasosartan, a long-acting angiotensin II AT1 receptor blocker, in the treatment of patients with essential hypertension

Abstract: This paper summarizes tolerability data for 1420 patients with essential hypertension who were enrolled in eight double-masked, controlled clinical trials and who received tasosartan, a long-acting, nonpeptidic angiotensin II AT 1 receptor blocker A total of 2084 patients were included in all treatment groups in these studies Patients were treated with tasosartan at doses ranging from 10 to 600 mg, over periods of 3 to 16 weeks, except for one study with a 6-day treatment period Tasosartan was administered once daily (seven studies) or twice daily (one study) No adverse events occurred at a significantly greater frequency in tasosartan-treated patients than in patients who received placebo Headache, the most frequently reported adverse event, occurred significantly less frequently among tasosartan-treated patients than among those taking placebo (19% and 28%, respectively) The following adverse events (tasosartan and placebo groups) were reported by at least 3% of tasosartan-treated patients: asthenia (7% in each group), pharyngitis (7% in each group), dizziness (7% and 5%, respectively), infection (6% and 7%, respectively), rhinitis (4% and 6%, respectively), pain (4% in each group), diarrhea (4% in each group), nausea (3% in each group), and dyspepsia (3% and 2%, respectively) Cough occurred with a similar frequency in the tasosartan group and in the placebo group (2% and 3%, respectively) Peripheral edema occurred in 27% of tasosartan-treated patients and 34% of the patients who received placebo Hyperglycemia occurred in

A 42-year-old man with hypertension.

Abstract: Dr Delbanco: Mr J is a 42-year-old African-American man first diagnosed with hypertension when he was 28 years old. He is married, lives in an apartment in the inner city of Boston with his wife and child, and works in an accounting department. He has health insurance through a managed care plan. His family history for hypertension is striking. His father died at the age of 69 years of complications of hypertension, with multiple strokes and congestive heart failure. His mother died at age 55 years of complications of hypertension and congestive heart failure. His 6 siblings do not have hypertension, but 3 have asthma. After being found hypertensive, Mr J underwent an evaluation for secondary causes, including physical examination, urinalysis, electrolytes, serum urea nitrogen, creatinine, serum creatinine, and thyroid function tests; all findings were normal. He stopped smoking in 1991 after a 12 pack-year history and has not smoked