PubMed Health⌕ Search

Biomedical subjects

E D Frohlich

Publications and source records attributed to E D Frohlich.

At least 163 records · Page 9Linked to original sources
PubMed1989

Overview of hemodynamic and non-hemodynamic factors associated with left ventricular hypertrophy.

The role of the heart in hypertension has finally emerged as a major issue of cardiovascular concern by the clinician, physiologist, pharmacologist, biochemist, and molecular biologist. This discussion provides an overview of the present state of knowledge and current areas of investigation in this active area of broad interest. Generally, these relate to: the active participation of the heart (e.g. hemodynamic, humoral, autocrine/paracrine); the adaptive response of the heart (i.e. hemodynamic); non-hemodynamic relationships (vis-a-vis, age, race, gender, humoral, coexistent disease); and current thoughts on mechanisms of so-called regression of left ventricular hypertrophy. Several antihypertensive classes of compounds are characterized by decreasing cardiac mass and left ventricular wall thicknesses. The angiotensin converting enzyme inhibitors are included among these agents; their physiological effects in producing "regression" are under active study as are the mechanisms responsible for these changes. These concerns are no longer of incidental or theoretical interest but have major impact on selection of antihypertensive therapy and the management of the patient with hypertension. Thus, the heart may participate actively in the pathogenesis and maintenance of the disease; it adapts to the vascular disease hemodynamically; but in this regard the response has both positive beneficial concerns as well as negative implications as an independent risk factor. These latter concerns should be explored in great depth before conclusions are made with respect to the long-term implications of antihypertensive therapy on the heart.

Antihypertensive Agents↗
PubMed1989

Effect of ATP and amiloride on ANF binding and stimulation of cyclic GMP accumulation in rat glomerular membranes.

We investigated ANF binding and stimulation of cGMP accumulation in isolated rat glomerular membranes in the presence and absence of amiloride and ATP. Amiloride enhanced high affinity binding of ANF without affecting its stimulation of cGMP. In contrast ATP decreased binding and decreased basal cGMP accumulation without affecting the ability of ANF to stimulate cGMP. These data indicate that ANF binding and stimulation of cGMP accumulation can be regulated independently supporting further the concept of receptor heterogeneity in renal glomerular membranes.

Adenosine Triphosphate↗
PubMed1989

The evolution of antihypertensive therapy: an overview of four decades of experience.

Hypertension is a major public health problem amendable to treatment. Numerous large scale clinical trials have demonstrated that effective, sustained control of elevated arterial pressure to a level below 140/90 mm Hg results in reduced cardiovascular morbidity and mortality. Over the past 4 decades antihypertensive drug therapy has evolved from a stepwise, but physiologically rational, selection of agents to specific programs tailored to individualized therapy for specific clinical situations. This evolution has taken place because of a greater understanding of the pathophysiology of hypertensive diseases, the development of new classes of antihypertensive agents that attack specific pressor mechanisms, and the ability to wed these concepts into a rational and specific therapeutic program. Thus, with the currently available spectrum of antihypertensive therapy, we are now able to select treatment for special patient populations utilizing a single agent and, therefore, we can protect the heart, brain and kidneys and maintain organ function without exacerbating associated diseases. These benefits are clear-cut and have resulted in many millions of patients becoming the beneficiaries of this transfer of careful, painstaking and purposeful investigative experiences into clinical practice.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Different hemodynamic effects of atrial natriuretic factor and nitroglycerin in rats with congestive heart failure.

Atrial natriuretic factor (ANF) decreases cardiac filling pressure, suggesting that diminished venous return is an important mechanism for the associated reduction in cardiac output. To determine whether ANF reduces cardiac preload through venodilation in congestive heart failure (CHF), we compared the hemodynamic effects of ANF-(99-126) with those of the venodilator nitroglycerin in conscious rats with CHF induced by coronary artery ligation previously. Depending on the extent of myocardial infarction, rats were subdivided into two groups: 1) mild or 2) severe CHF. Incremental intravenous infusions of ANF (0.1, 0.25, 0.5 micrograms.kg-1.min-1) or nitroglycerin (2, 5, 10 micrograms.kg-1.min-1) were administered for 20 min at each dose. Both agents reduced cardiac filling pressures. There was no change in cardiac output or arterial pressure at any dose of ANF in rats with severe CHF, but cardiac output decreased at higher ANF doses in rats with mild CHF. In contrast, nitroglycerin produced no change in cardiac output at any dose in either CHF group, although it decreased arterial pressure at the higher doses in rats with severe CHF. ANF increased whereas nitroglycerin decreased hematocrit in both CHF groups. The ANF-induced hematocrit increase also occurred in those rats with vesicovenous shunts designed to prevent volume contraction induced by diuresis. These data suggest that ANF and nitroglycerin decreased cardiac filling pressure through different hemodynamic mechanisms. The known venodilator action of nitroglycerin was associated with decreased hematocrit, suggesting enhanced transcapillary fluid migration. However, ANF produced an opposite effect on fluid migration as demonstrated by an increased hematocrit, suggesting a mechanism other than venodilation must be operative in reducing cardiac filling pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Angiotensin converting enzyme inhibitors. Present and future.

The angiotensin converting enzyme (ACE)-inhibiting agents have emerged with the diuretic agents, beta-adrenergic receptor-blocking agents, and calcium antagonists as therapeutic options for major consideration during the initial treatment of hypertensive patients. These compounds antagonize a potent pressor mechanism underlying hypertensive disease. The ACE inhibitors curtail the generation of the potent octapeptide angiotensin II; in addition, degradation of the potent vasodilator bradykinin is inhibited. Hemodynamically, ACE inhibitors reduce arterial pressure through a decreased total peripheral resistance that is unassociated with reflex stimulation of the heart or expansion of intravascular volume. The arteriolar dilation accounting for the decreased vascular resistance seems to occur in each target organ of the disease. Unlike the direct-acting smooth muscle vasodilators or adrenergic inhibitors, ACE inhibitors dilate the efferent as well as the afferent glomerular arterioles and thereby reduce glomerular hydrostatic pressure and renal filtration fraction, even though renal blood flow and glomerular filtration rate are preserved. The ACE-inhibiting compounds not only reduce left ventricular afterload in hypertension but also diminish cardiac mass and wall thicknesses. The mechanism(s) for some of these actions have not yet been defined precisely, but they undoubtedly involve the autocrine/paracrine actions of the renopressor system and their effects in the cellular biologic events of vascular smooth muscle and the cardiac myocyte. It seems plausible and exciting that the "more local" renin-angiotensin systems will be exploited by those ACE inhibitors yet to be synthesized, which will result in new applications for this class of pharmacological agents.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Atrial natriuretic factor effects on cyclic nucleotides in a human renal cell line.

The natriuretic effects of atrial peptide hormones have been attributed, at least in part, to their stimulation of guanylate cyclase activity in renal cell membranes. The effects of atrial natriuretic factor (ANF) on stimulation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) accumulation were investigated in cloned human kidney tumor (hKT) cells and parent cells from a human renal tumor epithelial cell line (SK-NEP-1). Human ANF-(99-126) (10(-6)M) stimulated (p less than 0.001) cellular cGMP accumulation in a dose-dependent manner from a basal level of 0.26 +/- 0.04 to 3.73 +/- 0.81 pmol/mg protein/5 mi (mean +/- SEM, n = 13). ANF stimulation of cGMP accumulation was specific, in that high concentrations (10(-6)M) of atriopeptin I [rat ANF-(103-123)], angiotensin II, arginine vasopressin, and amiloride (10(-4)M) did not increase basal cGMP. Amiloride (10(-4)M) enhanced (p less than 0.01, n = 6) the ANF stimulation of cGMP accumulation (1.24 +/- 0.39 pmol/mg protein/5 min), particularly at low doses of ANF (10(-10)M) where stimulation by ANF without amiloride (0.34 +/- 0.08 pmol/mg protein/5 min) was barely distinguishable from a basal level (0.19 +/- 0.02 pmol/mg protein/5 min) of cGMP accumulation. The stimulatory effect of ANF (1.59 +/- 0.07 pmol/mg protein/5 min) was attenuated (0.75 +/- 0.06 pmol/mg protein/5 min, p less than 0.01, n = 6) by preincubation of the cells with pertussis toxin but not by cholera toxin. ANF (4.56 +/- 0.93 pmol/mg protein/5 min, n = 8) did not affect cAMP accumulation (4.32 +/- 0.98 pmol/mg protein/5 min) in hKT cells. This is the first report of an ANF responsive human renal cell line, and its use should facilitate investigation of ANF-receptor interactions.

Atrial Natriuretic Factor↗
PubMed1989

Pathophysiology of hypertension: effects of calcium antagonists on heart and kidney.

Hypertension is a multifactorial disease that is manifested hemodynamically by an increased total peripheral resistance that is more or less uniformly distributed throughout the organ circulations, especially in its target organs, the brain, heart, and kidney. The vasoconstriction involves venules as well as arterioles. The increased afterload that is imposed upon the left ventricle results in the development of concentric hypertrophy. This may be complicated by a preload component early in hypertension or in patients who are volume-dependent (e.g., obesity, blacks). Eventually, if not treated, dysrhythmias, sudden death, or cardiac failure may supervene. The kidney becomes affected by progressive failure in function related to hemodynamic impairment secondary to afferent, as well as efferent, arteriolar constriction, which increases glomerular hydrostatic pressure. If at all possible, antihypertensive therapy should not be associated with intravascular volume expansion or reflex cardiac stimulation. Calcium antagonists reduce arterial pressure through a fall in vascular resistance without expanding volume or inordinately stimulating the heart. Left ventricular afterload is diminished with associated decrease of left ventricular mass. Moreover, renal blood flow increases while filtration fraction and glomerular hydrostatic pressure diminishes. Thus, these agents approach the ideal in reversing the pathophysiological complications of the disease.

Calcium Channel Blockers↗
PubMed1989

Calcium antagonists for initial therapy of hypertension.

A new class of antihypertensive agents has emerged for clinical consideration in the initial treatment of hypertension. These calcium antagonists are rapidly absorbed and reduce arterial pressure very promptly by antagonizing the pathophysiologic hallmark of the disease: an increased vascular resistance. Moreover, in reducing arterial pressure by means of arteriolar dilation, these agents do so without expanding intravascular volume and without inordinately stimulating the heart through reflex mechanisms. Vascular resistance is reduced in each of the major target organs of the disease: the heart, brain, and kidney. Reduction of coronary vascular resistance should be of particular value in patients with increased myocardial oxygen demands (e.g., with coronary arterial disease or with ventricular hypertrophy). Reduction of renal vascular resistance should be especially valuable for patients with renal functional impairment as a result of hypertensive vascular disease or with associated renal parenchymal diseases. In this respect, these agents reduce renal vascular resistance while maintaining glomerular filtration rate and reducing renal filtration fraction; these changes should reduce glomerular hyperfiltration and may inhibit promotion of glomerulosclerosis. Diltiazem may be of particular value because it may produce these effects while increasing renal blood flow. Clearly these agents reverse cerebral constriction and might be expected to improve blood flow to the brain; however, further study is anticipated and necessary.

Calcium Channel Blockers↗
PubMed1988

Hemodynamic, humoral and volume findings in systemic hypertension with isolated ventricular septal hypertrophy.

To analyze the hemodynamic, endocrine and volume characteristics of isolated septal hypertrophy (ISH) in established systemic hypertension, 22 patients with ISH were compared to 23 patients with symmetric hypertrophy and to 28 without left ventricular (LV) hypertrophy. Mean arterial pressure and 24-hour ambulatory pressure readings did not differ between the 2 groups. At the same level of arterial pressure, patients with ISH had a high cardiac index (p less than 0.02) and a faster heart rate (p less than 0.05); consequently, total peripheral resistance was decreased (p less than 0.05). Although there was no change in intravascular volume, central blood volume was expanded (p less than 0.02), and the ratio of central to peripheral blood volume was increased (p less than 0.02), thereby indicating peripheral venoconstriction. Patients with isolated ISH had greater responses of diastolic pressure and heart rate (p less than 0.05) to isometric stress than the other 2 groups. A hyperdynamic circulatory state is a hemodynamic hallmark of ISH in early essential hypertension that might be produced by increased sympathetic activity.

Adult↗
PubMed1988

Immediate and short-term cardiovascular effects of a new converting enzyme inhibitor (lisinopril) in essential hypertension.

The immediate and short-term effects of lisinopril, a new converting enzyme inhibitor, on systemic and regional hemodynamics, cardiac structure and function and humoral indexes were evaluated in 10 patients with mild to moderate essential hypertension. A single oral dose of 5 mg lisinopril reduced mean arterial pressure from 118 to 104 mm Hg (p less than 0.01) and significantly increased (p less than 0.05) all load-dependent indexes of ventricular function (i.e., ejection fraction, velocity of circumferential fiber shortening and fractional fiber shortening rate). After 10 to 12 weeks of once-daily administration of lisinopril, mean arterial pressure remained reduced over a full 24-hour period (p less than 0.01), and was mediated through arteriolar dilation as expressed by the close correlation (r = 0.93, p less than 0.01) between changes in mean arterial pressure and changes in total peripheral resistance. Cardiac index decreased from 3.06 to 2.68 liters/min/m2 (p less than 0.01) without correlation to the decrease in arterial pressure (r = 0.06). Despite this reduction in cardiac index, renal blood flow increased from 861 to 1,053 ml/min (p less than 0.05) and renal vascular resistance decreased from 14 to 9 units (p less than 0.01). Left ventricular mass index decreased from 124 to 109 g/m2 (p less than 0.05), and left ventricular function remained unchanged. Thus, the decrease in arterial pressure produced by lisinopril was associated with improved renal hemodynamics and reduced left ventricular mass.

Adult↗
PubMed1988

Hemodynamic comparison of diltiazem and TA-3090 in spontaneously hypertensive and normal Wistar-Kyoto rats.

Systemic and regional hemodynamic effects of 2 benzothiazepine derivatives, diltiazem and its congener TA-3090, were studied both acutely and chronically in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. All hemodynamic data were obtained in the conscious state using the reference sample radiomicrosphere method. Mean arterial pressure was reduced significantly with both immediate and more long-term treatment with both drugs in the SHR. The hypotensive action of TA-3090 was about 3 times as potent as diltiazem. The pressure reduction with both drugs was associated with a decrease in total peripheral resistance. TA-3090 seemed to have lesser effect on heart rate than diltiazem, although its net effect on cardiac output was similar, remaining unchanged in each study group. After intravenous injection, both diltiazem and TA-3090 significantly reduced vascular resistances of the major target organs of hypertension: heart, brain and kidneys in SHR. However, with prolonged treatment, organ vascular resistances seemed to be nonuniformly distributed. Intrarenal hemodynamics revealed significant differences between SHR and WKY rats after intravenous diltiazem and prolonged treatment with TA-3090. Thus, efferent as well as afferent arteriolar resistance decreased and therefore calculated glomerular capillary hydrostatic pressure decreased in SHR; however, efferent resistance and glomerular pressure remained unchanged in WKY rats. In contrast, intravenous TA-3090 evoked no such differences. Thus, diltiazem as well as TA-3090 dilated efferent as well as afferent arterioles in the SHR but not in the WKY rats. This effect was associated with a reduction in glomerular capillary pressure, preventing glomerular hyperfiltration through efferent arteriolar dilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Cardiac involvement in hypertension.

Despite improved patient detection and pharmacologic therapy, the effect of treatment of hypertension on mortality from coronary artery-related events remains unresolved. Left ventricular (LV) hypertrophy, a known consequence of hypertension, is associated with an excess mortality independent of other known cardiovascular risk factors. Recently, LV hypertrophy accompanying hypertension has been associated with ominous ventricular arrhythmias. However, it does not necessarily follow that regression of LV hypertrophy will reduce this increased mortality. Diastolic dysfunction, manifested by reduced ventricular distensibility of the hypertrophying left ventricle, appears to be an early characteristic of the hypertensive heart since echocardiographic techniques have demonstrated diastolic filling abnormalities in untreated essential hypertensives even before significant LV hypertrophy appears. Not all antihypertensive agents diminish LV mass and improve diastolic dysfunction. Certain sympatholytic agents, calcium antagonists, beta-adrenergic blockers, and the angiotensin-converting enzyme inhibitors appear to diminish LV hypertrophy. However, future studies are needed to determine if these agents that appear to reverse findings of LV hypertrophy and improve diastolic dysfunction will also reduce risk of coronary artery disease and related events.

Cardiomegaly↗
PubMed1988

Hypertension and stress.

This study explores the relationship of chronic stress to hypertension. The study included 127 hospitalized and 134 outpatients of a stress treatment program and 129 "normal" persons in the general population. All subjects were matched for age, sex, and race. After three days of hospitalization, there was a 17.3% incidence of hypertension in the hospitalized patients when hypertension was defined as blood pressure levels greater than 140/90 mmHg. These data compare with a 5% and 13% incidence of hypertension in the outpatient stress and "normal" groups, respectively. The National Health Survey of 1962 indicated that 18% of the population were hypertensive. Our data indicate that the incidence of hypertension was no greater in a diagnostically established group of hospitalized stress patients than in the less stressed outpatient or an otherwise "normal" group. The frequently expressed notion that tension and chronic stress predispose a population to essential hypertension is not confirmed by this analysis.

Adolescent↗