Search PubMed⌕ Search

Biomedical subjects

M A Weber

Publications and source records attributed to M A Weber.

At least 19 recordsLinked to original sources
PubMed1995

Low-dose drug combination therapy: an alternative first-line approach to hypertension treatment.

To investigate the concept that the initial treatment of hypertension with low doses of two antihypertensives that have different modes of action and additive effects may achieve control of blood pressure and minimize the dose-dependent adverse effects seen with conventional monotherapy, a randomized, double-blind parallel group dose-escalation study was conducted. After a 4 to 5 week placebo washout period, 218 men and women with diastolic blood pressure between 95 and 114 mm Hg were randomly allocated to take: amlodipine (2.5 to 10 mg), enalapril (5 to 20 mg), and the low-dose combination of bisoprolol (2.5 to 10 mg) with 6.25 mg of hydrochlorothiazide (HCTZ). All drugs were administered once daily, titrated to optimal response, and taken for a total of 12 weeks. Blood pressure was measured 24 hours after dose. The response rates (either a diastolic blood pressure < or = 90 mm Hg or a decrease of diastolic pressure > or = 10 mm Hg) were 71% for bisoprolol-6.25 mg HCTZ, 69% for amlodipine, and 45% for enalapril. The mean decreases in systolic/diastolic blood pressure from baseline were 13.4/10.7, 12.8/10.2, and 7.3/6.6 mm Hg for bisoprolol-6.25 mg HCTZ, amlodipine, and enalapril, respectively. The mean change with enalapril was less than the other drugs (p < 0.01), although the once-daily dosing of enalapril and the maximum dose of 20 mg might not have been optimal for this agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Ambulatory blood pressure monitoring: clinical uses.

Ambulatory monitoring is a strategy that may effectively address the phenomenon of "white coat" hypertension and determine whether the peaks and troughs that typify circadian variations should be considerations in blood pressure management. In selected patients, ABPM may indeed be useful both for diagnosing hypertension and for monitoring response to therapy.

Blood Pressure Monitors↗
PubMed1992

Dependency of arterial compliance on circulating neuroendocrine and metabolic factors in normal subjects.

Reduced arterial compliance is now recognized as a feature of hypertension. Similarly, metabolic factors such as insulin, catecholamines and lipids are also associated with hypertension. This study explores the possibility that these neuroendocrine and metabolic factors may separately influence arterial compliance. Proximal compliance (aorta and large arteries) and distal compliance (small arteries and arterioles) were measured in 57 volunteers (30 hypertensive and 27 normotensive subjects, mean age 45 years). Compliance was quantified by analysis of arterial pulse wave contours obtained intraarterially together with hemodynamic estimates. Proximal compliance correlated with plasma insulin (r = -0.49; p less than 0.001), norepinephrine (r = -0.50; p less than 0.002), triglycerides (r = -0.39; p less than 0.01), total cholesterol (r = -0.33; p = 0.02) and high-density lipoprotein cholesterol (HDL) (r = 0.37; p less than 0.02). Similarly, distal compliance correlated with insulin (r = -0.37; p less than 0.02), triglycerides (r = -0.39; p less than 0.01), total cholesterol (r = -0.38; p less than 0.01) and HDL (r = 0.51, p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Impact of left ventricular hypertrophy on blood pressure responses to exercise.

It is claimed that exaggerated blood pressure (BP) responses to exercise are predictive of future hypertension and may also be indicative of left ventricular (LV) hypertrophy. The relation between LV hypertrophy and maximal exercise BP was examined in 35 normal male volunteers and 65 untreated hypertensive male patients. Multiple stepwise regression analysis revealed that preexercise systolic BP was the major determinant of maximal exercise systolic BP (r = 0.52; p less than or equal to 0.0001), indicating that higher baseline BP predicted higher exercise BP. However, hypertensive patients with LV hypertrophy had the smallest increases in systolic BP with exercise. Accordingly, there was an inverse relation between LV muscle mass and systolic BP responses to exercise in these patients (r = -0.34; p = 0.005). When compared with normotensive subjects, hypertensive patients had lower measures of maximal oxygen uptake and exercise heart rates (p = 0.01). This may indicate lower cardiac performance at maximal exercise and explain the reduced capacity of hypertensive patients with LV hypertrophy to increase systolic BP with exercise. Neither baseline nor exercise BPs correlated with LV mass; instead, the model of regression analysis indicated that body weight was the principal determinant of LV mass. Contrary to previous reports, exaggerated exercise BPs were not associated with LV hypertrophy in hypertensive or normotensive patients.

Adult↗
PubMed1992

Heredity and hypertension: impact on metabolic characteristics.

This study was performed to evaluate the possible role of heredity in the clinical characteristics of hypertension. Metabolic, endocrine, and renal measurements were compared in subjects with normal blood pressure who had a family history of hypertension (n = 60) with those of subjects with normal blood pressure who did not have a family history of hypertension (n = 48). The groups were matched for age (mean, 44 +/- 2 years and 45 +/- 2 years) and blood pressure (127 +/- 1/77 +/- 1 mm Hg and 127 +/- 2/77 +/- 1 mm Hg). The following parameters were higher in the patients with a family history of hypertension than in those without. Plasma insulin concentrations (14.1 +/- 1.1 vs 10.8 +/- 1.0 microU/ml; p less than 0.05), insulin-glucose ratio (0.15 +/- 0.01 vs 0.11 +/- 0.010; p less than 0.05), norepinephrine concentrations (315 +/- 24 pg/ml vs 208 +/- 20 pg/ml; p less than 0.01), plasma renin activity (2.1 +/- 0.2 ng Angl/ml/hr vs 1.6 +/- 0.2 ng Angl/ml/hr; p less than 0.02), total cholesterol levels (217 +/- 8 mg/dl vs 197 +/- 0.3 mg/dl; p less than 0.05), creatinine clearance (125 +/- 9 ml/min vs 96 +/- 8 ml/min; p less than 0.01), and albumin excretion rate (3.2 +/- 0.3 micrograms/min vs 2.6 +/- 0.3 micrograms/min; p = 0.1). Moreover, patients with a family history of hypertension had smaller increases in systolic blood pressure during treadmill exercise (55 +/- 3 mm Hg vs 64 +/- 3 mm Hg; p less than 0.03). There were no differences in echocardiographic left ventricular mass index between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Circulatory and extracirculatory effects of angiotensin-converting enzyme inhibition.

The antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors cannot be fully explained by their actions on the circulating renin-angiotensin system (RAS). Agents such as captopril or enalapril maintain efficacy during long-term therapy even when plasma concentrations of converting enzyme or angiotensin II are not fully suppressed. Components of the entire RAS exist at several sites, thereby making it possible for drugs to produce effects at extracirculatory locations. An ACE inhibitor such as quinapril that has a comparatively short plasma concentration half-life binds strongly to plasma ACE as well as to ACE in key tissues including artery wall, heart, and kidney. The effects of ACE inhibition on the tissue RAS are of potential importance in fully explaining the blood pressure-lowering effects of these drugs. ACE inhibitors might also reduce blood pressure by blocking nonhemodynamic actions of angiotensin II. They affect vascular properties by increasing compliance of arteries and they act on baroreceptors and central regulatory mechanisms. Furthermore, ACE inhibitors affect other neuroendocrine systems, including aldosterone, kinins, and prostaglandins; attenuation of sympathetic activity can contribute further to their antihypertensive properties. Actions independent of circulating renin effects do not necessarily require plasma ACE inhibition throughout a 24-hour period. Sustained antihypertensive effects by drugs with short durations of plasma ACE inhibition give credibility to therapeutic targets beyond the circulating RAS.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Clinical experience with the angiotensin II receptor antagonist losartan. A preliminary report.

The nonpeptide angiotensin II (AII)-receptor antagonist losartan is a selective blocker of the pressor effects of AII. It is now being evaluated as an anti-hypertensive drug in multicenter clinical trials in the United States and other countries. Preliminary inpatient studies have shown that after 5 days of treatment, losartan--in doses of 50, 100, and 150 mg--is significantly more effective than placebo in decreasing blood pressure, and has efficacy similar to that of the angiotensin-converting enzyme (ACE) inhibitor enalapril. Large-scale dose-ranging studies in ambulatory hypertensive patients have shown that 10- and 25-mg losartan doses have brief effects in lowering blood pressure, but when given once daily, 50 mg is the minimal dose needed to produce significant day-long decreases in blood pressure. Interestingly, higher doses do not appear to exhibit greater efficacy; however, the effects of these doses are all similar to those of enalapril (20 mg once daily). Losartan's long duration of action is documented by ratios of trough (end of 24-h dosing interval) to peak antihypertensive effects, which are consistently above 50%. Clinical experiences thus far have indicated a low incidence of adverse events. Preliminary animal and in vitro investigations have shown that losartan produces beneficial effects on cardiac function, renal function, and survival that are similar to those of ACE inhibitors. Additional studies are now under way to define more fully the cardiovascular and metabolic profiles of losartan.

Angiotensin Receptor Antagonists↗
PubMed1992

Fosinopril: a new generation of angiotensin-converting enzyme inhibitors.

Fosinopril, the first agent in a new chemical class of phosphorus-containing angiotensin-converting enzyme (ACE) inhibitors, has unique pharmacologic properties. Fosinopril administration leads to complete inhibition of plasma ACE activity for 12-24 h. In patients with normal renal function, approximately equal amounts of the drug are eliminated via the hepatic and renal routes. With worsening renal function, increasing amounts of fosinopril are eliminated hepatically. This dual elimination allows for the administration of fosinopril using the same starting dosage to any patient, regardless of renal function. Fosinopril may provide end-organ protection against the effects of hypertension and antihypertensive therapy; this drug potentially protects the kidney by increasing renal functional reserve, while maintaining cardiac left ventricular performance. Moreover, despite marked blood reductions, cerebral blood flow is maintained. Controlled trials show that fosinopril in single daily doses of 10-40 mg is efficacious and safe for the long-term treatment of hypertension. At these doses, favorable responses were seen in up to 80% of patients. Fosinopril is equally effective in elderly as well as younger patients and works in black as well as in nonblack patients. The incidence of adverse events does not differ significantly between fosinopril- and placebo-treated patients. Fosinopril represents a clinically useful agent for the treatment of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Left ventricular hypertrophy and antihypertensive therapy.

Left ventricular hypertrophy is more common in hypertensive individuals than in normotensive persons. Its presence in hypertensive patients is associated with an increased incidence of ventricular arrhythmias, myocardial infarction, congestive heart failure, stroke and cardiovascular mortality. Echocardiography is more sensitive than electrocardiography in detecting left ventricular hypertrophy. Echocardiographic evidence of this condition in patients with borderline hypertension may identify those who need treatment. Weight reduction and drug therapy can prevent or reverse ventricular hypertrophy in hypertensive patients. Recent studies suggest that some antihypertensive drugs are more effective than others in reducing left ventricular hypertrophy. These agents include beta-adrenergic blockers, angiotensin converting enzyme inhibitors, calcium channel blockers and sympatholytic agents. Although little evidence exists to show that reduction of left ventricular mass decreases cardiovascular morbidity and mortality, avoidance of antihypertensive agents that may aggravate hypertrophy would seem prudent.

Antihypertensive Agents↗
PubMed1992

A dose escalation trial comparing the combination of diltiazem SR and hydrochlorothiazide with the monotherapies in patients with essential hypertension.

A multicentre, randomised, placebo-controlled parallel group study comparing various doses of the combination diltiazem SR (DTZ SR)/hydrochlorothiazide (HCTZ) with the monotherapies was performed to delineate the optimal antihypertensive dosage of the two drug combinations. The study was carried out in 298 patients with mild to moderate essential hypertension (stable supine diastolic blood pressure, DBP, greater than or equal to 95 and less than or equal to 110 mmHg). After a single-blind placebo lead-in period lasting 4-6 weeks to establish stable baseline BP, the patients were randomised to receive either placebo (n = 75), HCTZ (n = 76), DTZ SR (n = 72), or the combination of DTZ SR/HCTZ (n = 75). There were three 4-week evaluation periods with forced escalation of therapy as follows: HCTZ (6.25, 6.25, 12.5 mg twice daily), DTZ SR (60, 90, 120 mg twice daily), and the combination of DTZ SR/HCTZ (60/6.25, 90/6.25, 120/12.5 mg twice daily). DTZ SR/HCTZ (120/12.5 mg) produced statistically significantly greater reductions in supine DBP compared with each monotherapy and placebo. The lower doses of DTZ SR/HCTZ (60/6.25 mg and 90/6.25 mg) produced statistically significantly greater supine DBP reductions compared with DTZ SR monotherapy and placebo, but not compared with HCTZ monotherapy. A comparison of reduction in supine DBP between evaluation periods demonstrated a dose-response relationship for the combination therapy in reducing BP over the dosage range studied. Adverse clinical and laboratory events were not significantly different between the therapies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Norepinephrine amplifies angiotensin II-induced vasoconstriction in rabbit femoral artery.

Several reports have focused on the ability of angiotensin II to amplify vascular contractile responses to norepinephrine, but none have determined whether norepinephrine enhances angiotensin II-induced vasoconstriction. Measuring isometric contraction in isolated rabbit femoral artery rings, we have found that the angiotensin II-induced contractile response was amplified in the presence of a threshold contraction to norepinephrine, as manifested by a 2.9-fold leftward shift of the midpoint of the concentration-response curve with no change in the maximal response. This amplification was attenuated markedly by nifedipine (0.1 microM), a calcium channel antagonist, implicating calcium channel activation in the amplification phenomenon. Precontracting the smooth muscle with a threshold concentration of angiotensin II had no enhancing effect on further angiotensin responses, indicating that the norepinephrine-induced amplification was due to a specific action of norepinephrine, rather than to a precontraction itself. In experiments in which the angiotensin II response was diminished by the presence of the noncompetitive angiotensin II antagonist [Sar1 Ala8]angiotensin II (0.3 microM), norepinephrine affected the angiotensin II response primarily by increasing the maximal response attainable. Prazosin (0.1 microM) both blocked the norepinephrine threshold contraction and abolished completely the amplification. However, when the norepinephrine concentration was increased until a threshold contraction was elicited in the presence of a fixed concentration of prazosin, amplification of the angiotensin II response was restored. These results indicate that norepinephrine exerts its amplifying effect on angiotensin II via activation of alpha-1 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

Cardiovascular and metabolic characteristics of hypertension.

Hypertension is now seen as a broader condition than high blood pressure alone. Large-scale epidemiologic studies have established that high blood pressure is associated with an increased risk of cardiovascular events, but clinical trials of antihypertensive therapy have shown an inconsistent reduction in major cardiovascular endpoints. Importantly, the incidence of coronary disease has been reduced to only a small extent, suggesting that factors beyond high blood pressure are important in the genesis of atherosclerotic disease in hypertensive patients. It is evident, for example, that patients with hypertension have an exaggerated vulnerability to the consequences of lipid abnormalities. Moreover, it has recently been established that hypertension is characterized by insulin resistance and altered glucose tolerance. As a result, high plasma concentrations of insulin produce proliferative effects on vascular smooth muscle and connective tissue, and they may adversely affect the lipid profile. The left ventricle is also involved in hypertension--independent of blood pressure. There is growing evidence that there are increases in the muscle mass of the left ventricle and changes in its diastolic filling characteristics at the very early stages of hypertension. The arterial circulation is similarly involved, for alterations in structure or function, reflected by diminished arterial compliance, can be demonstrated prior to the appearance of clinical hypertension. Treatment designed to protect hypertensive patients from cardiovascular events must not only be based on blood pressure, but must take into account all the components of the hypertension syndrome.

Blood Glucose↗
PubMed1991

Left ventricular diastolic filling alterations in normotensive young adults with a family history of systemic hypertension.

To characterize the cardiovascular consequences of a history of hypertension in first-degree relatives in normotensive young adults, 72 normotensive (diastolic blood pressure [BP] less than 90 mm Hg) healthy volunteers (age 18 to 30 years) were studied with 2 dimensionally guided M-mode echocardiography, pulsed Doppler echocardiography, and 2-hour automated BP monitoring. Of the 72 subjects, 19 (12 men and 7 women) had a family history of hypertension and were compared with 19 subjects without a family history of hypertension who were matched for systolic BP and gender. There were no detectable differences in 2-hour average BP, left ventricular (LV) mass or wall thickness, or echocardiographic systolic functional indexes between subjects with and without a family history of hypertension. Doppler-derived diastolic functional indexes demonstrated more prominent late diastolic filling in subjects with a family history of hypertension. Late diastolic transmitral flow time and flow velocity integral were greater (132 +/- 24 vs 117 +/- 17 ms, p less than 0.05; and 2.5 +/- 0.7 vs 1.9 +/- 0.5 cm, p less than 0.01, respectively). To measure possible gender-related effects of a family history of hypertension, the men and women were analyzed separately. The 12 men with a family history of hypertension had greater peak late (40 +/- 0.9 vs 31 +/- 0.8 cm/s, p less than 0.02) and ratio of late-to-early (0.64 +/- 0.19 vs 0.46 +/- 0.10, p less than 0.01) transmitral flow velocities and greater late transmitral flow velocity integrals (2.6 +/- 0.8 vs 1.9 +/- 0.5 cm, p less than 0.05) than the matched male control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Hypertension with concomitant conditions: the changing role of beta-adrenoceptor blockade.

Hypertension often is associated with concomitant conditions such as chronic obstructive lung disease, diabetes mellitus, ischemic heart disease, and peripheral vascular disease. Moreover, other cardiovascular risk factors, including dyslipidemias and abnormalities of glucose and insulin metabolism, are common in patients with hypertension. Conventional beta-blockers used for antihypertensive therapy can have adverse effects in patients with airway disease, diabetes, and peripheral vascular disease, and can exaggerate the other risk factors. Newer beta-blockers such as celiprolol, which have selective partial agonist activity expressed at beta 2-receptors, appear to avoid these problems. Celiprolol exhibits antianginal and antihypertensive efficacy without adversely effecting left ventricular systolic function or exercise performance. It also may cause regression of left ventricular hypertrophy. The stimulatory action of celiprolol on vascular beta 2-receptors enhances regional flow and may increase walking distance in patients with claudication. The reduction in renal vascular resistance demonstrated by this drug is associated with preservation of renal blood flow and function. Spirometric measurements of airway function are unchanged during celiprolol treatment. Similarly, there are no adverse effects on lipid or glucose concentrations. These new developments in beta-blocker pharmacology indicate that this class of agents could be used in patients with hypertension with concomitant diseases or risk factors other than high blood pressure.

Adrenergic beta-Antagonists↗
PubMed1991

Immediate blood pressure effects of the renin inhibitor enalkiren and the angiotensin-converting enzyme inhibitor enalaprilat.

The antihypertensive effects of the renin inhibitor enalkiren were compared with those of the angiotensin-converting enzyme inhibitor enalaprilat in 17 hypertensive patients (14 white, 3 black; mean age 57 years), whose renin systems had been stimulated by diuretic pretreatment. Patients were studied on 3 separate in-hospital days. On the first study day patients received placebo alone. On day 2 they received intravenous bolus doses of enalkiren (0.03 to 1.0 mg/kg), and on day 3, intravenous bolus doses of enalaprilat (0.625 to 1.25 mg). Each agent reduced systolic (p less than 0.01) and diastolic (p less than 0.01) blood pressure (BP) from baseline levels. The acute decrease in systolic BP of 18.5 +/- 0.4 mm Hg during enalkiren tended to be greater (p less than 0.01) than the decrease of 12.6 +/- 0.7 mm Hg during enalaprilat. Decreases in diastolic BP during enalkiren (11.9 +/- 0.4 mm Hg) were also slightly greater (p less than 0.1) than those during enalaprilat (9.2 +/- 0.4 mm Hg). Based on prestudy plasma renin activity (PRA), patients were divided into "high" renin (PRA greater than 3.5 ng angiotensin l/ml/hr; n = 6) and "low/normal" renin (less than 3.5 ng angiotensin l/ml/hr; n = 11) groups. Reductions in diastolic BP in the "high" renin group during enalkiren (30 +/- 5/20 +/- 3 mm Hg) tended to be greater (p less than 0.07) than those during enalaprilat (23 +/- 7/14 +/- 1 mm Hg); differences were not significant in the "low/normal" group (12 +/- 2/7 +/- 2 and 7 +/- 2/8 +/- 1 mm Hg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗