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Biomedical subjects

M A Weber

Publications and source records attributed to M A Weber.

At least 91 records · Page 5Linked to original sources
PubMed1995

Relationship of left ventricular structure to maximal heart rate during exercise.

Previous investigators using clinical, hemodynamic, or exercise parameters to predict maximal exercise heart rate (HRmax) have demonstrated age to be the major determinant. Regression coefficients have ranged from -0.3 to -0.6, leaving approximately two thirds of the variance in HRmax unexplained. Because cardiac size and function are directly related to stroke volume and should influence HRmax, we studied 114 male subjects (aged 19 to 73 years) with two-dimensional and M-mode echocardiography who underwent maximal treadmill testing with respiratory gas analysis. Seventy-three were normotensive (diastolic BP < 95 mm Hg) and 41 were hypertensive. As in previous studies, HRmax was inversely related to age (HRmax = 199-0.63[age], r = -0.47, p < 0.001). M-mode left ventricular (LV) diastolic dimension (LVD) added significantly to the explanation of the variance in HRmax (r = -0.57, p < 0.001) (HRmax = 236 - 0.72 [age]-6.8 [LVD]). Thus, the larger the heart, the lower the HRmax. No other echocardiographic measurement or derived parameter added significantly to the explanation of the variance in HRmax. To evaluate the effects of hypertension on HRmax, we studied hypertensives and normotensives separately. Only age was significantly related to HRmax in the normotensives (r = -0.50, p < 0.001). In the hypertensive subjects, however, both age and relative wall thickness (RWT) (which describes LV wall thickness in relation to LV chamber size) were significantly related to HRmax. Age explained 45% of the observed variance in HRmax (r = 0.67, p < 0.001) and RWT added modestly (9%) but significantly to the relationship (HRmax = 173-0.96[age]+94 [RWT], p < 0.001), together explaining 54% of the variance observed in HRmax. Thus, HRmax is inversely related to LVD and patients with larger ventricles achieve lower HRmax. In hypertensives, the amount of LV muscle mass in relation to chamber size is an additional predictor of HRmax. However, despite controlling for age, sex, and cardiovascular disease, and the inclusion of echocardiographic indices of cardiac size and function, a large portion of the variance in HRmax could not be explained. The unexplained variance in HRmax is most likely due to intersubject variability in resting cardiac size, volume, function, and other as yet undefined factors.

Adult↗
PubMed1995

Hypertension in the elderly: 24 h ambulatory blood pressure results from a placebo-controlled trial.

Calcium channel blockers are increasingly used to treat hypertension in elderly patients. To assess the effects of low-dose, long-acting verapamil on blood pressure (BP) and quality of life (QOL) in elderly patients, verapamil 120-240 mg of placebo was given once daily for 8 weeks to 76 patients aged > or = 60 years. After a 4-week placebo wash-out period, patients with a sitting DBP of 95-110 mm Hg and a mean daytime (6 am to 6 pm) ambulatory DBP > or = 90 mm Hg were entered into the study. Twenty four-hour BP monitoring as well as QOL self-assessment and digit span testing of cognitive function were performed at the end of the placebo wash-out and double-blind treatment periods. Patients treated with verapamil showed a significant decrease in mean whole-day BP, while those treated with placebo showed a small increase in BP. Treatment differences between the two groups in SBP and DBP were each statistically significant (P < 0.01). Significant differences were also seen when the 24 h period was divided into daytime and night-time readings. Both QOL and digit span testing scores were unchanged from baseline for verapamil-treated patients and were not different from the placebo-treated group. The results of this study demonstrate consistent and significant decreases in BP throughout the 24 h period with no adverse effects on QOL or cognitive function this this formulation of verapamil in elderly hypertensive patients.

Aged↗
PubMed1995

The evolving paradigm of hypertension.

Although it is convenient to think of hypertension in its renal, epidemiologic, and vascular eras, a new perspective is rapidly coming to the forefront. As we become more critical in evaluating the performance of our health care systems, it is obvious that the major problems in hypertension do not lie entirely with unsolved problems of physiology or therapeutics. Rather, we have come to realize that a large number of our hypertensive patients remain inadequately treated or, even more commonly, are receiving no treatment at all. Outcomes research into strategies for enhancing patient compliance with treatment and research dealing with other issues associated with clinical effectiveness are emerging as leading priorities.

Humans↗
PubMed1995

Controlling blood pressure throughout the day: issues in testing a new anti-hypertensive agent.

Lessons learned from ambulatory blood pressure (BP) monitoring strongly influence the development of new anti-hypertensive drugs. Efficacy should be demonstrated not only in the conventional clinical setting, but also throughout the full 24 h day, including the important early morning hours near the end of dosing intervals. Preservation of the circadian pattern, including appropriate day/night BP differences, may be a further important goal of therapy. The reproducibility of ambulatory monitoring measurements, together with the absence of placebo effects with this technique, adds greatly to its power and efficiency. Moreover, the use of ambulatory monitoring to accurately diagnose hypertension and exclude non-confirmed or white coat hypertensives from clinical trials adds further sensitivity to quantifying drug action. This technique was recently applied to the evaluation of the new angiotensin II receptor antagonist losartan. Hypertensive patients diagnosed by ambulatory monitoring were divided into four groups: placebo, losartan 50 mg once daily, 100 mg once daily or 50 mg twice daily. Compared with placebo, which had no effect, all three losartan regimens decreased SBP and DBP significantly. There was no difference in efficacy between the two once daily regimens, although 50 mg twice daily was slightly more effective than 50 mg once daily but not statistically significantly different from 100 mg once daily. However, all losartan groups exhibited sustained BP reductions throughout the 24 h dosing interval and preserved the circadian BP patterns. Ambulatory monitoring was thus able to accurately quantity the efficacy and the key chronobiological aspects of anti-hypertensive therapy with losartan in an efficient and cost-effective manner.

Adult↗
PubMed1994

Prostaglandin E2 and prostacyclin inhibit the production and secretion of endothelin from cultured endothelial cells.

Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor yet identified. This peptide plays an important role in the regulation of arterial tone, in part through its interaction with endogenous vasodilator compounds. To understand the interactions of endothelin with the vasoactive prostaglandins (PGs), we determined the effects of prostaglandin E2 (PGE2), prostacyclin (PGI2), and thromboxane A2 on ET-1 synthesis and secretion from cultured bovine aortic endothelial cells and on ET-1 action in aortic smooth muscle cells. Both PGE2 and PGI2 (vasodilator prostaglandins) caused an approximately 40% inhibition of basal ET-1 secretion and a 50% inhibition of serum-stimulated ET-1 secretion in a dose-related and time course fashion. In contrast, the vasoconstrictor prostaglandin, thromboxane A2, had no effect on ET-1 secretion. PGE2 and PGI2 similarly inhibited the basal production of new ET-1 protein (translation) by 40-50% and inhibited the basal steady-state mRNA expression of ET-1 in bovine aortic endothelial cells by 60-70%. Both prostaglandins also caused an approximately 55% inhibition of ET-1 transcription, as shown by chloramphenicol acetyltransferase reporter studies. PGE2 and PGI2 strongly stimulated cGMP generation; both the PG stimulation of cGMP and the inhibition of ET-1 secretion and translation were reversed by LY83583, a general inhibitor of cGMP generation. The PG-induced inhibition of ET-1 secretion and translation was also reversed by KT5823, an inhibitor of cGMP-dependent protein kinase, but not by (Rp)-adenosine cyclic 3':5'-monophosphate, an inhibitor of protein kinase A activation. PGE2 and PGI2 also inhibited both basal and ET-1-stimulated DNA synthesis in aortic smooth muscle cells by approximately 45% through a cGMP-dependent mechanism. Therefore, two endogenous PGs, known to be important vasodilators in vivo, significantly inhibit the transcription, translation, secretion, and action of ET-1. We propose that the vasodilator action of the PGs results, in part, from their ability to inhibit the production of this potent vasoconstrictor.

Alkaloids↗
PubMed1994

Effect of chelation treatment with dimercaptosuccinic acid (DMSA) on lead-related blood pressure changes.

An elevation in mean blood pressure was found in rats treated with low lead (0.01%) for 6 months and then only water for an additional 6 months (discontinuous low lead). No change in blood pressure was found in rats similarly treated with high lead (0.5%) (discontinuous high lead). Administration of DMSA (0.5% in drinking water), for 5 days every 2 months following cessation of lead administration, resulted in a significant lowering of blood pressure in both groups of animals. In the low-lead but not the high-lead group, this was associated with an increase in plasma cyclic GMP (acting as a second messenger for endothelium-derived relaxing factor, EDRF) and a decrease in the plasma concentration of a 12-kDa hypertension-associated protein. Plasma endothelin-3 (ET-3) levels were decreased in discontinuous high-lead rats, increased in discontinuous low-lead rats, but were unaltered by DMSA treatment. We infer that the elevated blood pressure in the discontinuous low-lead rats is related to an increase in the putative vasoconstrictors, ET-3 and the hypertension-associated protein, without a change in the vasodilator, EDRF. With DMSA treatment, plasma cyclic GMP in low-lead rats increased above normal, and the hypertension-associated protein decreased, resulting in lowered blood pressure. DMSA was shown to act as an antioxidant in vitro. Thus the DMSA effect on plasma cGMP (EDRF) may occur via a scavenging effect on EDRF-inactivating reactive oxygen species.

Animals↗
PubMed1994

Measuring hypertensive cardiovascular risk: the vascular overload concept.

Hypertensive cardiovascular risk may be related primarily to vascular overload, the sum of three vascular abnormalities: increased arteriolar resistance, increased large-artery stiffness, and the effect of increased early pulse-wave reflection. A method for quantifying vascular overload as an index can be derived from measurements of mean arterial pressure and pulse pressure. Several lines of evidence support the hypothesis that abnormal artery stiffness and early pulse-wave reflection become larger components of vascular overload as the duration and severity of hypertension increase. Moreover, these studies suggest that vascular overload is a true indicator of hypertensive cardiovascular risk. Increased systolic blood pressure is a surrogate for vascular overload in young and middle-aged hypertensive subjects. Increased pulse pressure and decreased diastolic pressure are superior to increased systolic pressure as surrogates for vascular overload in geriatric isolated systolic hypertension. By itself, diastolic blood pressure is difficult to interpret and may be an epiphenomenon. Therefore new therapeutic goals, are control of systolic pressure in the young and of pulse pressure in the elderly.

Adult↗
PubMed1994

Extended-release felodipine in patients with mild to moderate hypertension. Felodipine ER Dose-Response Study Group.

Two hundred eighty-six patients with mild to moderate hypertension who had untreated diastolic blood pressure while seated of 95 to 115 mm Hg were randomized to receive placebo or once-daily doses of 2.5, 5, or 10 mg of the dihydropyridine calcium channel blocker felodipine extended release (ER). Blood pressure was measured 24 hours after dosing (at trough). Mean reductions in diastolic blood pressure after 8 weeks of double-blind treatment were significantly greater in each of the ER felodipine treatment groups (2.5, 5, and 10 mg ER felodipine: -7.8, -9.5, and -11.3 mm Hg, respectively) than in the placebo group (-5.3 mm Hg). The effect was dose dependent for both diastolic and systolic blood pressure. Moreover, much of the peak antihypertensive effect was still present at trough, confirming the 24-hour efficacy of the drug. Felodipine was well tolerated.

Administration, Oral↗
PubMed1994

Coronary heart disease and hypertension.

Coronary disease is a frequent outcome of hypertension. Although clinical trials with conventional antihypertensive agents have shown that the incidence of other complications of hypertension, such as stroke or congestive heart failure, is reduced as predicted, they have failed to show the expected reductions in coronary events. A partial explanation may lie in the fact that hypertension typically consists of a syndrome of inherited metabolic and cardiovascular abnormalities, and treatment that focuses primarily on blood pressure control without taking into account other factors that contribute to atherosclerotic disease can have only limited protective effects. The coronary hypothesis in hypertension extends this reasoning into three separate components. First is an intrinsic tendency to excessive proliferative and hypertrophic activity within vascular tissue, presumably reflecting growth-promoting activity stimulated by increased endocrine and local paracrine effects; next is the impact of the commonly encountered concomitant risk factors, including high blood pressure, that exaggerate and accelerate development of underlying atherosclerotic lesions; and finally hemodynamic factors, including increased variability and sustained elevations of blood pressure, that can destabilize vascular lesions and precipitate acute events. Treatment of these hemodynamic factors in elderly patients whose underlying vascular changes are already well advanced is likely to reduce vascular endpoints effectively, but a broader-based therapeutic approach is required for younger patients, in whom the ongoing proliferative and risk factor aspects of their potential coronary disease must also be targeted.

Antihypertensive Agents↗
PubMed1994

Modern strategies to prevent coronary sequelae and stroke in hypertensive patients differ from the JNC V Consensus Guidelines.

In recent years, government agencies of many countries have established consensus guidelines for the evaluation and treatment of hypertension. Once published, guidelines tend to be perceived as directives by a variety of health care providers. Unfortunately, these guidelines often do not reflect the practices of most hypertension experts. This report summarizes the opinions of seven hypertension experts concerning the impact of "official" guidelines on clinical practice. In addition, the individual therapeutic recommendations of these panel members are summarized. Their different treatment strategies reflect the diversity of first rate treatment plans that aim to reduce the cardiovascular sequelae in individual patients with essential hypertension. Most importantly, not one of these seven treatment strategies followed the "preferred" treatment of the U.S. guidelines, which recommend diuretics and beta-blockers as first-line therapy. The present authors approach the treatment of hypertension as a means to reduce cardiovascular events. Thus, reduction of blood pressure is not the most important therapeutic endpoint. The panel believes that whereas many different drugs can produce effective blood pressure reduction, the modern primary goal of antihypertensive drug therapy is to select a regimen most likely to prolong the quality and duration of life. In real terms, this means that the primary goal of treatment is the prevention of the major vascular sequelae of hypertension (heart attack, ventricular remodeling, hypertrophy, heart failure, and stroke) that shorten useful life. There are a number of effective hypertensive treatments, which can be selected based on individual patient requirements. However, many consensus guidelines do not allow the flexibility required to optimize individual patient treatment. As a result, health care providers should not feel compelled to regard the preferences of "official" guidelines as the best, modern, state-of-the-art therapy for an individual patient. All seven experts who are deeply involved in the daily care of patients preferred drugs other than beta-blockers and diuretics (the Joint National Committee [JNC] choices) for first-line therapy of hypertension.

Cardiovascular Diseases↗
PubMed1994

Characterization of a low molecular weight Na-K-ATPase inhibitor of urinary origin.

It has been demonstrated that expansion of extracellular fluid volume induces the release of a low-molecular-weight natriuretic and sodium-potassium-activated adenosine triphosphatase inhibiting hormone (NKAI). In this study, we used a highly purified hormone extracted from pooled hypertensive urines (u-NKAI). Like ouabain, this compound was found to be a potent inhibitor of the sodium-potassium-activated adenosine-triphosphatase and potassium-stimulated paranitrophenyl phosphatase enzyme systems as well as a vasoconstrictor in vitro. In contrast to ouabain, which is a competitive inhibitor of both enzyme systems with respect to potassium, u-NKAI is noncompetitive. Furthermore, u-NKAI differs from ouabain by its lack of cross-reactivity with digoxin antibodies. In addition, whereas ouabain binds to both high-affinity and low-affinity binding sites on the sodium-potassium-activated adenosine-triphosphatase enzyme in the absence of potassium, u-NKAI binds only to the low-affinity binding sites. This study demonstrates that the highly purified u-NKAI, although ouabain-like in certain respects, is not an "endogenous ouabain."

4-Nitrophenylphosphatase↗
PubMed1994

Diagnosis of mild hypertension by ambulatory blood pressure monitoring.

BACKGROUND: Between 20% and 30% of patients with clinically diagnosed hypertension have normal blood pressure (BP) values during automated ambulatory 24-hour BP monitoring. It has not been clear, however, whether these patients can be regarded as normotensive or whether they should be treated in the same way as confirmed hypertensive patients. METHODS AND RESULTS: Ambulatory BP monitoring was performed in 88 normal control subjects and 171 hypertensive patients (office diastolic BP > or = 90 mm Hg on three visits; never treated or off treatment for more than 6 months). Hypertensive patients were classified as nonconfirmed or white coat (n = 58) if their 24-hour diastolic averages were < 85 mm Hg and at least 15 mm Hg lower than their office values. For comparisons, white coat patients were pair-matched with normal subjects by 24-hour diastolic averages and sex, and by similar age and weight; there were 40 such pairs. White coat patients were likewise pair-matched with confirmed hypertensive patients by identical office BPs (51 pairs). Participants were studied by individualized treadmill testing, Doppler echocardiography, and assays of resting plasma catecholamines, upright plasma renin and aldosterone, and lipid, glucose, and insulin concentrations. Because of the matching, compared with normal subjects, patients with white coat hypertension and normal subjects had identical 24-hour BP averages. The white coat patients exhibited slightly greater variability among individual readings (obtained each 15 minutes) throughout the day [P < .05]), but there were no differences in hemodynamic responses to exercise. Plasma norepinephrine (P < .05), renin and aldosterone (P < .01 for each), and insulin and low-density lipoprotein cholesterol levels (P < .01 for each) were higher in the white coat group, as were left ventricular septal wall (P < .05) and muscle mass (P = .07) echocardiographic measurements. When compared with the confirmed hypertensive patients, the white coat patients had higher renin (P < .01) but were otherwise similar. Within the white coat group, plasma norepinephrine correlated with total cholesterol and triglycerides (P < .05 for each), and aldosterone correlated with left ventricular mass (P < .01); there were no significant correlations within the normal control subject or confirmed hypertension groups. CONCLUSIONS: Patients with white coat hypertension differ in metabolic, neuroendocrine, and cardiac findings from normal control subjects and have greater BP variability. These changes appear to be mediated by heightened activity of the sympathetic and renin-angiotensin systems. Although these characteristics could reflect an alerting reaction in the clinic due to awareness of their diagnosis, the white coat hypertensive patients also have evidence for additional, more-sustained differences from normal subjects. Thus, this condition appears to be a true variant of hypertension.

Adult↗
PubMed1994

A repressive coping style protecting from emotional distress in low-renin essential hypertensives.

OBJECTIVE: To investigate the relationship between the behavioural characteristics and specified subgroups of patients with essential hypertension. DESIGN AND METHODS: Fifty-four patients were classified into groups with a high (n = 9), normal (n = 35) or low plasma renin activity (n = 10), and were compared with 20 normotensive subjects by psychological tests. Standardized tests were used to measure anger expression, defensiveness and the subjects' psychological status (e.g. anxiety, depression). RESULTS: A repressive coping style, defined by a high defensiveness and low anxiety levels, was found significantly more often in patients with low than in patients with high plasma renin activity and normotensive subjects. The patients with high plasma renin activity scored significantly higher on suppressed anger, anxiety and interpersonal sensitivity than did those with low plasma renin activity. The scores of the normal plasma renin activity group were similar to those of the normotensive group. CONCLUSIONS: The results underline that there is not one hypertensive 'personality'. Whereas the patients with a high plasma renin activity appear to be more susceptible to emotional conflicts, the patients with low plasma renin activity report low emotional distress and maintain an apparently well-adjusted facade.

Adaptation, Psychological↗
PubMed1994

Lower dose diuretic therapy in the treatment of patients with mild to moderate hypertension.

Indapamide (Lozol), an indoline antihypertensive drug with diuretic and vasodilating activities, was evaluated in 195 patients with mild to moderate essential hypertension (sitting DBP between 95 and 110 mmHg) in a multicentre, randomised, double-blind, parallel-group design trial. A four week single-blind placebo wash-out period was followed by an eight week double-blind period. Patients were randomised to indapamide 1.25 mg/day or to placebo. The primary efficacy endpoint was the mean change in sitting DBP from baseline to week 8. Ninety patients in the placebo group (93%) and 82 patients (84%) in the indapamide group completed the eight weeks of double-blind therapy. Indapamide produced a mean (SE) decrease in sitting DBP of 7.4 (0.63) mmHg (from 100.1 to 92.8 mmHg) compared with a decrease of 3.6 (0.75) mmHg (from 99.6 to 95.8 mmHg) produced by placebo (p < 0.0001). Indapamide and placebo also produced mean decreases in standing DBP of 6.8 (0.75) and 2.8 (0.77) mmHg, respectively (p = 0.0002), in sitting SBP of 11.1 (1.18) and 3.2 (1.35) mmHg, respectively (p = 0.0001) and in standing SBP of 11.4 (1.29) and 4.0 (1.43) mmHg, respectively (P = 0.0002). Reduction in BP of > or = 10 mmHg or to a DBP of < or = 90 mmHg was more frequent (P = 0.0005) among indapamide (46.6%) compared with placebo (23.7%) treated patients. During the eight week double-blind treatment period, incidence rates for all adverse experiences and for drug-related adverse experiences were similar between the two treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Controversies in the diagnosis and treatment of hypertension: a personal review of JNC V.

In January 1993 the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure published its fifth report (JNC V). The report highlighted the importance of systolic hypertension and recommended that hypertension should be diagnosed--regardless of age--when systolic blood pressure readings are consistently > or = 140 mm Hg. JNC V reflected the opinion in JNC IV that several drug classes--including diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, and alpha blockers--are suitable for initiating antihypertensive therapy. However, JNC V gave preference to diuretics and beta blockers because these drug classes have been shown to reduce the incidence of stroke and cardiovascular events in clinical trials; similar studies with the newer drug classes have not yet been completed. This recommendation is highly controversial because the benefits of diuretic and beta-blocker use are most evident in the elderly, and the beneficial effects of these drugs on the incidence of coronary events are relatively modest. Further, growing experience with ACE inhibitors and calcium antagonists shows that these agents lack the metabolic disadvantages of older agents and can exhibit antiatherosclerotic and antihypertrophic vasoactivity. Although to date the clinical benefits of the newer agents have been documented in conditions other than hypertension, the data are persuasive and indicate a probability that these drugs will improve prognosis in hypertensive patients. JNC V also emphasized lifestyle modifications; however, even when they decrease blood pressure, dietary and other nonpharmacologic strategies have not been shown to lower the incidence of clinical events.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1993

Comparison of bisoprolol with atenolol for systemic hypertension in four population groups (young, old, black and nonblack) using ambulatory blood pressure monitoring. Bisoprolol Investigators Group.

The antihypertensive effects of drugs are partly determined by characteristics of the patients treated. A randomized, double-blind study used 24-hour ambulatory blood pressure (BP) monitoring to compare the effects of 2 beta blockers, bisoprolol (10 to 20 mg; n = 107) and atenolol (50 to 100 mg; n = 96), administered once daily in 4 population groups. After a 4-week placebo period, patients with an office diastolic BP between 95 and 114 mm Hg were stratified according to race and age, and were randomly assigned to treatment with bisoprolol or atenolol for 8 weeks. BP averages measured by automated monitoring for the 24-hour periods were compared between groups. In elderly patients, the reductions in both average 24-hour systolic and diastolic BP were greater with bisoprolol than with atenolol (13 +/- 3/13 +/- 1 mm Hg [n = 23] vs 4 +/- 2/6 +/- 1 mm Hg [n = 30]; p < 0.01). Similarly, bisoprolol produced greater reductions in average 24-hour diastolic BP than did atenolol in nonblack patients (16 +/- 2/12 +/- 1 mm Hg [n = 85] vs 12 +/- 2/9 +/- 1 mm Hg [n = 83]; p = 0.02). Bisoprolol and atenolol were similar in the black (10 +/- 5/9 +/- 3 mm Hg [n = 22] and 10 +/- 6/6 +/- 3 mm Hg [n = 13], respectively) and young (15 +/- 1/11 +/- 1 mm Hg [n = 84] and 16 +/- 2/10 +/- 1 mm Hg [n = 66], respectively) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Hypertension as a risk factor syndrome: therapeutic implications.

Reduction of blood pressure as the only therapeutic goal of antihypertensive treatment may no longer be appropriate. 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 artery 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 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. New therapeutic strategies should be aimed at the full spectrum of hypertension-related changes. Because the renin-angiotensin system can contribute to the structural and functional cardiovascular characteristics of this condition, such agents as angiotensin-converting enzyme inhibitors may be especially effective in preventing or reversing these abnormalities and are emerging as a treatment of choice for hypertension.

Animals↗