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Biomedical subjects

S Oparil

Publications and source records attributed to S Oparil.

At least 37 records · Page 2Linked to original sources
PubMed2000

A randomized trial of improved weight loss with a prepared meal plan in overweight and obese patients: impact on cardiovascular risk reduction.

OBJECTIVE: To assess the long-term effects of a prepackaged, nutritionally complete, prepared meal plan compared with a usual-care diet (UCD) on weight loss and cardiovascular risk factors in overweight and obese persons. DESIGN: In this randomized multicenter study, 302 persons with hypertension and dyslipidemia (n = 183) or with type 2 diabetes mellitus (n = 119) were randomized to the nutrient-fortified prepared meal plan (approximately 22% energy from fat, 58% from carbohydrate, and 20% from protein) or to a macronutrient-equivalent UCD. MAIN OUTCOME MEASURES: The primary outcome measure was weight change. Secondary measures were changes in blood pressure or plasma lipid, lipoprotein, glucose, or glycosylated hemoglobin levels; quality of life; nutrient intake; and dietary compliance. RESULTS: After 1 year, weight change in the hypertension/dyslipidemia group was -5.8+/-6.8 kg with the prepared meal plan vs -1.7+/-6.5 kg with the UCD plan (P<.001); for the type 2 diabetes mellitus group, the change was -3.0+/-5.4 kg with the prepared meal plan vs -1.0+/-3.8 kg with the UCD plan (P<.001) (data given as mean +/- SD). In both groups, both interventions improved blood pressure, total and low-density lipoprotein cholesterol levels, glycosylated hemoglobin level, and quality of life (P<.02); in the diabetic group, the glucose level was reduced (P<.001). Compared with those in the UCD group, participants with hypertension/dyslipidemia in the prepared meal plan group showed greater improvements in total (P<.01) and high-density lipoprotein (P<.03) cholesterol levels, systolic blood pressure (P<.03), and glucose level (P<.03); in participants with type 2 diabetes mellitus, there were greater improvements in glucose (P =.046) and glycosylated hemoglobin (P<.02) levels. The prepared meal plan group also showed greater improvements in quality of life (P<.05) and compliance (P<.001) than the UCD group. CONCLUSIONS: Long-term dietary interventions induced significant weight loss and improved cardiovascular risk in high-risk patients. The prepared meal plan simultaneously provided the simplicity and nutrient composition necessary to maintain long-term compliance and to reduce cardiovascular risk.

Adult↗
PubMed2000

Estrogen attenuates integrin-beta(3)-dependent adventitial fibroblast migration after inhibition of osteopontin production in vascular smooth muscle cells.

BACKGROUND: Previous in vitro studies have suggested that estrogen attenuates the vascular injury response by modulating vascular smooth muscle cell (VSMC) expression of soluble factor(s) directing migration of adventitial fibroblasts. Previous in vivo studies have established a role for osteopontin (OPN) and its integrin receptors after vascular injury. In this study, we examined OPN expression in activated VSMCs, its modulation by estrogen, and its effects on adventitial fibroblast migration. In addition, the relative functional roles of beta(1)- and beta(3)-integrin-matrix interactions were examined. METHODS AND RESULTS: Primary cultures of VSMCs and adventitial fibroblasts were derived from female Sprague-Dawley rats. Serum-activated VSMCs expressed high levels of OPN mRNA and secreted protein that was effectively inhibited by estrogen treatment (10(-7) mol/L). Compared with VSMCs, fibroblasts expressed similar levels of integrins alphanu and beta(1) and higher levels of integrin-beta(3). Exogenous OPN (5.0 to 40 microg/mL) directed fibroblast migration in a dose-dependent fashion. Anti-beta(3)-integrin antibody (F11) pretreatment markedly inhibited adventitial fibroblast migration directed by exogenous OPN or VSMC-conditioned medium in a dose-dependent manner. In contrast, anti-beta(1)-integrin antibody (Ha2/5) did not affect fibroblast migration. Similarly, pretreatment with either linear or cyclic RGD peptides (10 to 1000 micromol/L) inhibited fibroblast migration directed by OPN or VSMC-conditioned medium in a dose-dependent manner. CONCLUSIONS: These observations suggest that estrogen indirectly attenuates integrin-beta(3)-dependent adventitial fibroblast migration after inhibition of OPN expression in VSMCs.

Animals↗
PubMed2000

Estrogen-induced vasoprotection is estrogen receptor dependent: evidence from the balloon-injured rat carotid artery model.

BACKGROUND: Previous studies have shown that estrogen (E2) is vasoprotective in multiple animal models of vascular injury, including mice with homologous disruptions of either the alpha or beta isoforms of the estrogen receptor (ER) gene, calling into question the ER dependency of the vasoprotective effect. This study used ICI 182,780, a nonselective ER antagonist, to test the hypothesis that the vasoprotective effect of E2 in the rat carotid injury model is ER mediated. METHODS AND RESULTS: Intact female Sprague-Dawley rats were divided into 4 groups and treated with the nonselective ER antagonist ICI 182,780 (ICI; 0.5, 1.5, or 5 mg. kg(-1). d(-1), subcutaneously [S.C.]) or vehicle, beginning before balloon injury of the right common carotid artery and continuing for 14 days afterward. Four groups of ovariectomized rats (OVX) were treated with 17beta estradiol (E2) (20 microgram. kg(-1). d(-1), S.C.) alone or combined with ICI 5 mg. kg(-1). d(-1), S.C.; with ICI 5 mg. kg(-1). d(-1) alone; or with vehicle according to a similar protocol. Two weeks after injury, rats were killed, and the carotid arteries were evaluated for neointima formation using morphometric analysis. ICI 182,780 blunted the E2-related protective effect and increased neointima formation in injured carotid arteries of intact female rats in a dose-dependent fashion. ICI had no effect on neointima formation in OVX, but addition of ICI to E2 in OVX blocked the inhibitory effect of exogenous E2 on neointima formation. CONCLUSIONS: These results indicate that the vasoprotective effect of E2 in the balloon-injured rat carotid artery model is mediated by ER.

Animals↗
PubMed2000

Direct in vivo evidence demonstrating neointimal migration of adventitial fibroblasts after balloon injury of rat carotid arteries.

BACKGROUND: Clinical and experimental evidence suggest that the adventitia participates in the response to endoluminal vascular injury. The current study used a direct approach to test the hypothesis that, after balloon injury of the rat carotid artery, adventitial fibroblasts migrate in a luminal direction and contribute to neointima formation. METHODS AND RESULTS: Primary syngeneic adventitial fibroblasts were stably transduced with retroviral particles coordinating expression of beta-galactosidase (LacZ) and introduced into the adventitia of right carotid arteries of rats immediately after balloon injury. At defined times after injury and fibroblast implantation, rats were euthanized, and arterial tissue was examined for detection of LacZ mRNA (reverse transcription polymerase chain reaction), DNA (polymerase chain reaction), and in situ enzymatic activity. LacZ expression was detected in the media 5 days postinjury and in both media and neointima at 7, 10, and 14 days postinjury. LacZ was undetectable in injured vessels that had not been seeded with transduced fibroblasts and was restricted to the adventitia in seeded vessels that were not injured. CONCLUSIONS: These observations provide direct demonstration of adventitial fibroblast migration into neointima of arteries after endoluminal injury.

Animals↗
PubMed2000

Effects of increased consumption of fluid milk on energy and nutrient intake, body weight, and cardiovascular risk factors in healthy older adults.

OBJECTIVE: To assess the impact of increased consumption of milk, without other dietary advice, on older adults' energy and nutrient intakes, weight, cardiovascular risk factors (blood pressure, plasma lipid levels), and quality of life. SUBJECTS/SETTING: Two hundred four healthy men and women, aged 55 to 85 years, who consumed fewer than 1.5 dairy servings per day were chosen from six US academic health centers. DESIGN: Randomized, controlled open trial. INTERVENTION: Advice to increase skim or 1% milk intake by 3 cups per day (n = 101) or to maintain usual diet (n = 103) for 12 weeks after a 4-week baseline period. MAIN OUTCOME MEASURES: Changes in energy and nutrient intake assessed from 3-day food records, body weight, blood pressure, and plasma lipid levels. STATISTICAL ANALYSES PERFORMED: Group-by-time analysis of variance with repeated-measures, chi 2 test. RESULTS: Compliance with the intervention was good. Compared with controls, participants in the milk-supplemented group significantly increased energy, protein, cholesterol, vitamins A, D, and B-12, riboflavin, pantothenate, calcium, phosphorus, magnesium, zinc, and potassium intakes. Prevalence of nutrient inadequacy, assessed for nutrients with Estimated Average Requirements, decreased among women in the milk group for magnesium (40% at baseline vs 13% at 12 weeks, P < .001) and vitamin B-12 (6% vs 0%, P < .05) and tended to decrease (P < .10) for protein and thiamin (women) and magnesium and vitamin B-6 (men). The milk group gained 0.6 kg more than control group (P < .01); however, weight gain was less than predicted, which suggests some compensation for the added energy from milk. Blood pressure decreased similarly over time in both groups. Total and low-density lipoprotein cholesterol levels, and the ratio of total cholesterol to high-density lipoprotein cholesterol, were unchanged. Triglyceride levels increased within the normal range in the milk group (P = .002). Quality of life scores were high at baseline and remained high throughout. APPLICATIONS/CONCLUSIONS: Older adults can successfully increase milk intake, thereby meaningfully improving their nutrient intakes. Dietitians can play a key role in disseminating this advice.

Aged↗
PubMed2000

The organum vasculosum of the lamina terminalis regulates noradrenaline release in the anterior hypothalamic nucleus.

Changes in either plasma sodium concentration or arterial pressure can differentially affect hypothalamic neurons. For instance, increases in plasma NaCl concentration decrease noradrenaline release from nerve terminals in the anterior hypothalamic nucleus, while increases in arterial pressure unrelated to an elevation in plasma NaCl enhance noradrenaline release in anterior hypothalamic nucleus. The present study tests the hypothesis that in the rat the organum vasculosum of the lamina terminalis (an osmosensitive area of the brain) detects rises in plasma NaCl concentration and conveys this information to anterior hypothalamic nucleus. The axons projecting from the organum vasculosum of the lamina terminalis to the hypothalamus were unilaterally cut immediately caudal to organum vasculosum of the lamina terminalis, and five days later, 3-methoxy-4-hydroxy phenylglycol (the major metabolite of noradrenaline in brain) was continuously monitored in the ipsilateral or contralateral anterior hypothalamic nucleus in response to an intravenous infusion of hypertonic saline. In spontaneously hypertensive rats, the infusion decreased the 3-methoxy-4-hydroxy phenylglycol concentration by 24+/-2% in the anterior hypothalamic nucleus contralateral to the lesion, and in control spontaneously hypertensive rats. In contrast, in the anterior hypothalamic nucleus ipsilateral to the lesion, hypertonic saline infusion caused a 58+/-3% increase in 3-methoxy-4-hydroxy phenylglycol. These data support the hypothesis that the organum vasculosum of the lamina terminalis is part of the circuit that transmits information concerning plasma NaCl concentration to anterior hypothalamic nucleus.

Animals↗
PubMed2000

Lowering of blood pressure and predictors of response in patients with left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint.

The Losartan Intervention For Endpoint (LIFE) reduction in hypertension study is a double-blind, prospective, parallel-group study comparing the effects of losartan with those of atenolol on the reduction of cardiovascular complications in patients (n = 9,194) with essential hypertension and with electrocardiographically (ECG) documented left ventricular hypertrophy (LVH). Baseline blood pressure was 174.4/97.8 mm Hg (mean), age 66.9 years, body mass index 28.0 kg/m2; 54.1% were women and 12.5% had diabetes mellitus. This population will be treated until at least 1,040 have a primary endpoint. After five scheduled visits and 12 months of follow-up, blood pressure decreased by 23.9/12.8 mm Hg to 150.5/85.1 mm Hg (target < 140/90 mm Hg). The mandatory titration level of < or = 160/95 mm Hg was reached by 72.1% of the patients. At the 12-month visit, 22.7% of all patients were taking blinded study drug alone, 44.3% were taking blinded drug plus hydrochlorothiazide (HCTZ), and 17.7% were taking blinded drugs plus HCTZ and additional drugs. Controlling for all other variables, patients in the US received more medication and had 2.4 times the odds of achieving blood pressure control than patients in the rest of the study (P < .001). Previously untreated patients (n = 2,530) had a larger initial decrease in blood pressure compared with those previously treated. Diabetics (n = 1,148) needed more medication than nondiabetics to gain blood pressure control. Only 13.9% of the patients had discontinued blinded study drug and 1.4% missed the revisit at 12 months. These data demonstrate both the successful lowering of blood pressure during 12 months of follow-up in a large cohort of patients with hypertension and LVH on ECG, but also emphasize the need for two or more drugs to control high blood pressure in most of these patients. Being previously treated and having diabetes were associated with less blood pressure response, whereas living in the US indicated better blood pressure control. It has been possible to keep most of these patients with complicated hypertension taking blinded study drug for 12 months.

Aged↗
PubMed2000

Factors affecting blood pressure responses to diet: the Vanguard study.

To study physiologic factors affecting the blood pressure (BP) response to nonpharmacologic maneuvers, fasting blood glucose, insulin, lipid and mineral levels, urinary mineral excretion, and the calcium regulating hormones parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D (1,25 (OH)2D) were measured in 71 unmedicated hypertensive (26 hypertensive only [HT], 45 hypertensive hyperlipidemic [HTHL]), and 87 normotensive hyperlipidemic (NTHL) control subjects before and during a 10-week multicenter, randomized controlled trial comparing a prepared meal plan (CCNW) with a self-selected diet (SSD) based on nutritionist counseling. Blood pressure fell to a greater extent in hypertensive versus normotensive subjects (-8+/-1/-5+/-1 v -2+/-1/-2+/-1 mm Hg, P < .0001/P < .0001), and on CCNW versus SSD diets (delta systolic BP [SBP]/delta diastolic BP [DBP], P = .033/P = .002). Diet-induced weight change was the strongest correlate of changes in BP (SBP: r = 0.360, P < .0001; DBP: r = 0.414, P < .0001), which, on multivariate analysis for deltaSBP, could partly be accounted for by diet-induced changes in fasting glucose (r = 0.215, P = .009) and cholesterol (r = 0.219, P = .006) levels. Independently of weight, diet-induced changes in SBP also were significantly related to concomitant changes in urinary excretion of potassium (r = -0.285, P = .001), magnesium (r = -0.254, P = .003), and calcium relative to sodium (r = -0.200, P = .021), but not to sodium per se; and to changes in serum potassium (r = -0.249, P = .002), phosphorus (r = -0.279, P = .001), PTH (r = 0.288, P = .0006), and 1,25 D (r = 0.202, P = .017). We conclude that the ability of diet to lower BP successfully may result from the additive contributions of multiple components. Independently of weight loss and the associated changes in circulating glucose and cholesterol, BP is influenced by the increasing provision of minerals such as potassium, magnesium, and calcium, perhaps by virtue of their suppressive effects on circulating vasoactive calcium regulating hormones.

Adult↗
PubMed2000

Newly emerging pharmacologic differences in angiotensin II receptor blockers.

Several angiotensin II receptor blockers (ARB) are currently available for the treatment of hypertension. These drugs share a common mechanism of action-antagonism of angiotensin II AT1 receptors; however, their receptor binding kinetics differ. Candesartan has a higher affinity for the AT1 receptor than all the other ARB. In addition, candesartan and irbesartan block the AT1 receptor with insurmountable antagonism, whereas losartan, valsartan, and eprosartan are competitive antagonists. The pharmacokinetics of these ARB also differ in terms of oral bioavailability, rate of absorption, metabolism, and route and rate of elimination. Both losartan potassium and candesartan cilexetil are prodrugs; however, losartan is partially converted into EXP3174 in the liver, whereas candesartan cilexetil is converted completely into candesartan during gastrointestinal absorption. On the basis of elimination half-lives, losartan, valsartan, and eprosartan may be classified as shorter acting and candesartan cilexetil and irbesartan as longer acting. Each drug effectively lowers blood pressure during once daily administration to patients with mild to moderate hypertension, with candesartan cilexetil requiring the lowest dosage and providing dose-dependent efficacy. Initial comparative clinical trials suggest that both candesartan cilexetil and irbesartan in the doses used are significantly more effective than losartan in lowering trough sitting diastolic blood pressure. It remains to be determined, however, whether the observed pharmacologic and pharmacokinetic differences among the members of the ARB class will have a clinically significant impact on long-term cardiovascular outcomes and reductions of cardiovascular mortality.

Angiotensin Receptor Antagonists↗
PubMed2000

Endothelial dysfunction in the pulmonary vascular bed.

The pulmonary endothelium modulates vascular tone by the release of endothelium-derived constricting (EDCF) and relaxing (EDRF) factors, among them endothelin-1, nitric oxide, prostacyclin, and putative endothelium-derived hyperpolarizing factors. Abnormalities in EDCF and EDRF generation have been demonstrated in a number of cardiopulmonary disease states, such as primary and secondary pulmonary hypertension, chronic obstructive lung disease, cardiopulmonary bypass, and congestive heart failure. An imbalance between EDCF and EDRF, termed "pulmonary endothelial dysfunction," may contribute to the alteration in vascular tone characteristic of pulmonary disease. The following review summarizes the present knowledge of the role of EDCF and EDRF in such processes with major focus on pulmonary endothelial dysfunction in hypoxia-induced pulmonary hypertension.

Animals↗
PubMed2000

Endothelin and pulmonary hypertension.

Biochemical and molecular biological evidence indicates that endothelin (ET)-1 and its receptors are selectively upregulated in the lung during exposure to hypoxia, while functional evidence indicates that ET-1 is a major mediator of hypoxia-induced pulmonary vasoconstriction and vascular remodeling. Hypoxia stimulates ET-1 gene transcription and peptide synthesis in cultured endothelial cells, and plasma ET-1 levels are increased in patients with primary pulmonary hypertension, and in humans exposed to high altitude, while immunoreactive ET-1 and ET-1 mRNA levels are increased in pulmonary artery endothelial cells of patients with primary pulmonary hypertension. Rats exposed to normobaric hypoxia exhibit increased pulmonary artery pressure, increased ET-1 peptide levels in plasma and lung, and selective increases in steady-state ET-1 and ET(A) and ET(B) receptor mRNA levels in lung but not in organs perfused by the systemic vasculature. The observations that both ET-1 and its major vascular smooth-muscle cell receptor are upregulated in response to hypoxia suggest that ET-1 may be a mediator of hypoxia-induced pulmonary hypertension. Moreover, hypoxic pulmonary vasoconstriction and vascular remodeling can be prevented and reversed by administration of either an ET(A)-selective or a combined ET(A) and ET(B) receptor antagonist. 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-receptor blockers may be useful in the treatment and prevention of hypoxic pulmonary hypertension in humans.

Animals↗
PubMed2000

Fenoldopam, a dopamine agonist, for hypertensive emergency: a multicenter randomized trial. Fenoldopam Study Group.

UNLABELLED: Despite successful therapies for chronic hypertension, hospital admissions for hypertensive emergency more than tripled between 1983 and 1992. OBJECTIVE: To examine the safety and efficacy of fenoldopam, the first antihypertensive with selective and specific action on vascular dopamine (DA1) receptors, in a clinical trial involving emergency department patients with true hypertensive emergencies. METHODS: Patients with a sustained diastolic blood pressure (DBP) of > or =120 mm Hg and evidence of target organ compromise were randomized in a double-blinded manner to one of four fixed doses of intravenous fenoldopam (0.01, 0.03, 0.1, or 0.3 microg/kg/min) for 24 hours. The primary endpoint was the magnitude of DBP reduction in each of the three higher-dose groups after four hours of fenoldopam treatment compared with the lowest-dose group. RESULTS: One hundred seven participants from 21 centers were enrolled, and 94 patients received fenoldopam. Evidence of acute target-organ damage included new renal dysfunction or hematuria (50%), acute congestive heart failure or myocardial ischemia (48%), and papilledema or grade III-IV hypertensive retinopathy (34%). The DBP decreased in a dose-dependent fashion, with significant differences between the 0.1- and 0.3-microg/kg/min groups compared with the lowest-dose group. Treatment was well tolerated, and there were no deaths or serious adverse events during follow-up, up to 48 hours. All patients were successfully transitioned to oral or transdermal antihypertensives with maintenance of blood pressure control. CONCLUSIONS: Fenoldopam safely and effectively lowers blood pressure in a dose-dependent manner in patients with hypertensive emergencies. Observations supporting potential risk factors for hypertensive emergency are discussed.

Adult↗
PubMed2000

[Calcium antagonists in cardiovascular disease. Clinical evidence from morbidity and mortality trials].

Calcium antagonists, particularly the newer, longer-acting agents, are clearly effective in reducing elevated blood pressure with minimal to modest adverse effect profiles, and are therefore used extensively. The goal of antihypertensive therapy, however, is not simply to reduce blood pressure, but also to reduce vascular injury due to hypertension. Prospective controlled clinical trials evaluating cardiovascular morbidity and mortality are needed to test calcium antagonists in patients with hypertension. This review summarises the design and, in some cases, the results of 7 trials (5 of them still ongoing) that have provided insight into the effects of moderate- to long-acting calcium antagonists on mortality and target-organ damage in patients with hypertension. The Systolic Hypertension in Europe (Syst-Eur) trial studied 4695 elderly patients with isolated systolic hypertension, and demonstrated significant reductions in stroke and all fatal and nonfatal cardiac end-points in patients randomised to nitrendipine versus placebo. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) compares the effects of standard diuretic treatment with 3 alternatives (amlodipine, lisinopril, and doxazosin) on the incidence of fatal coronary artery disease and nonfatal myocardial infarction in more than 42,000 hypertensive patients with additional cardiovascular risk factors. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) compares the effects of amlodipine +/- perindopril with atenolol +/- bendrofluazide on fatal coronary artery disease and nonfatal myocardial infarction in 18,000 high risk patients. The Controlled ONset Verapamil INvestigation of Cardiovascular End-points (CONVINCE) study is assessing the incidence of fatal or nonfatal myocardial infarction and stroke, and cardiovascular disease-related death in patients on controlled-onset extended-release verapamil compared with a standard regimen of hydrochlorothiazide or atenolol. The Nordic Diltiazem Study (NORDIL) also compares a calcium antagonist (diltiazem) with conventional antihypertensive drug treatment (diuretics or beta-blockers) with add-on therapy as needed, in preventing cardiovascular mortality or morbidity. The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) tests a similar hypothesis, examining the effects of amlodipine on atherosclerotic lesions. The African-American Study of Kidney Disease (AASK) trial is evaluating the effects of amlodipine in hypertensive patients with renal disease. These important clinical trials of different classes of antihypertensive agents are critical for optimising the treatment of hypertensive patients in order to prevent coronary artery disease and other vascular diseases in this new millennium. Importantly, these randomised trials are free of the major problems of observational studies, i.e., confounding by indication, and should fully address the concerns raised by observational studies and small, under-powered, randomised trials that calcium antagonists may have adverse effects on myocardial infarction, bleeding and cancer. To date, these trials in progress have provided no evidence to support these concerns.

Aged↗