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E D Frohlich

Publications and source records attributed to E D Frohlich.

At least 55 records · Page 3Linked to original sources
PubMed1999

State of the Art lecture. Risk mechanisms in hypertensive heart disease.

In this report, some of the underlying pathophysiological alterations associated with the independent risk from hypertensive heart disease and left ventricular hypertrophy are discussed. Emphasized are the classically described coronary hemodynamic alterations of decreased coronary blood flow and flow reserve with increased coronary vascular resistance and minimal coronary resistance; more recent concepts of endothelial dysfunction are emphasized. Additionally, increased collagen deposition within the ventricular walls and perivascularly participates importantly. These changes are exacerbated by the aging process and perhaps by increased dietary salt intake. Consequences of these functional and structural changes include further endothelial dysfunction, impairment of coronary hemodynamics, and ventricular contractile function (diastolic as well as systolic). The clinical consequences of these alterations are angina pectoris (with or without atherosclerosis), myocardial infarction, cardiac failure, lethal dysrhythmias, and sudden cardiac death. Thus, not all that is clinically recognized as "left ventricular hypertrophy" is true myocytic hypertrophy with structural remodeling; other important comorbid changes occur that directly affect risk, including ventricular fibrosis, impaired coronary hemodynamics, and endothelial dysfunction.

Aging↗
PubMed1998

Treatment guideline in the USA: hypertension in the elderly.

According to the JNC-5, at least six classes of antihypertensive agents have been synthesized and currently recommended for initial antihypertensive therapy in the USA for elderly patients. Each class is safe and effective in reducing arterial pressure, each has its own specific mechanism(s) of action that suppress specific pressor mechanisms, and each has its own side-effects which may be overcome by substituting a drug from another class of agents. In the case of adrenergic inhibitors, more specific agents have been introduced over the years. Each succeeding new class has obviated certain adverse effects of an earlier class. In the case of alpha-adrenergic receptor inhibitors, this concept is of particular value with the alpha 1A-receptor inhibiting compounds. The alpha 1-adrenergic inhibitors have special value for elderly patients with BPH as both hypertension and the prostatic disease can be treated with one compound. The alpha 1A-antagonists may have particular value in those patients in whom further reduction of arterial pressure is not desired and this obviously includes the normotensive elderly patient and the hypertensive patient whose blood pressure is already well-controlled by other agents.

Adrenergic alpha-Antagonists↗
PubMed1998

Hypertension.

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Aged↗
PubMed1998

Coronary hemodynamics in aging spontaneously hypertensive and normotensive Wistar-Kyoto rats.

OBJECTIVE: To delineate hypertension-related and age-related changes in coronary hemodynamics and to assess the role of myocardial (i.e. left ventricular) hypertrophy and cardiac fibrosis in inducing progressive deterioration of coronary flow reserve associated both with hypertension and with aging. METHODS: Systemic and coronary hemodynamics (using radionuclide-labeled microspheres), right ventricular, left ventricular, and aortic mass indexes, and ventricular hydroxyproline concentrations (an estimate of collagen) in normotensive Wistar-Kyoto and spontaneously hypertensive rats aged 22, 35, and 65 weeks were determined. RESULTS: Spontaneously hypertensive rats of all ages had greater left ventricular and aortic masses, greater collagen concentrations in both ventricles, a lower coronary flow reserve, and greater minimal coronary vascular resistance after administration of dipyridamole than did Wistar-Kyoto rats. Despite spontaneously hypertensive rats having only left ventricular hypertrophy, coronary hemodynamics were impaired to the same extent in both ventricles. Progressive increases in myocardial collagen concentration, decreases in coronary flow reserve, and increases in minimal coronary vascular resistance were observed in rats of both strains with aging. A positive correlation and linear regression between myocardial collagen concentration and minimal vascular resistance were found for both ventricles of rats of both strains. CONCLUSIONS: Both aging and hypertension adversely affected the coronary circulation; furthermore, these effects appeared to be additive. Cardiac fibrosis, but not hypertrophy, might play a role in progressive deterioration of coronary hemodynamics in aging and hypertension and could provide an explanation for the diastolic dysfunction encountered clinically in older patients with hypertension.

Aging↗
PubMed1998

Nephroprotective effect of antihypertensive drugs in essential hypertension.

BACKGROUND: Effective antihypertensive treatment has prevented target-organ involvement in hypertension, markedly reducing morbidity and mortality from strokes, coronary heart disease, cardiac failure, and hypertensive emergencies. However, the incidence of hypertension-related end-stage renal disease continues to increase, suggesting that therapeutic reduction in arterial pressure by itself is not sufficient to prevent the development of hypertensive renal failure. OBJECTIVE: To examine experimental and clinical data concerning the protective effect of reduction of arterial pressure on the progression of hypertension-related renal disease, and the evidence indicating that some antihypertensive agents may afford more nephroprotection, over and above that attributable to reduction of arterial pressure. RESULTS: Results of numerous studies clearly indicate that adequate control of arterial pressure, irrespective of the antihypertensive agent used, slowed the progression of renal disease. Results of some studies suggest that lowering arterial pressure below the level that is usually considered adequate has an additional beneficial effect by slowing the progression of renal injury. CONCLUSION: Results of a number of studies evaluating nephroprotective effects of various drugs and regimens have indicated that certain agents, most notably angiotensin converting enzyme inhibitors and their combination with calcium antagonists, afford more protection than do others at similar levels of reduction of arterial pressure. Results of still other studies suggest that certain agents that exert greater nephroprotection are more efficient at controlling arterial pressure. Therefore, further data are needed before any final conclusion can be drawn. However, it is clear that, in order to establish nephroprotection in patients with essential hypertension, the problem should not be further complicated by additional comorbid diseases such as diabetes mellitus.

Animals↗
PubMed1998

Renoprotective effects of felodipine and/or enalapril in spontaneously hypertensive rats with and without L-NAME.

To determine the renoprotective effects of a calcium antagonist (felodipine) and an angiotensin-converting enzyme (ACE) inhibitor (enalapril), alone or in combination, 10 groups of 19-week-old spontaneously hypertensive rats (SHR) (with or without N(G)-nitro-L-arginine methyl ester [L-NAME]) were studied using renal micropuncture techniques. Group 1 (control), group 2 (felodipine, 30 mg x kg(-1) x d[-1]), group 3 (enalapril, 30 mg x kg(-1) x d[-1]), and group 4 (felodipine plus enalapril, 15 mg x kg(-1) x d(-1) each agent) were studied after 3 weeks of treatment without L-NAME. L-NAME (50 mg/L) cotreatment was administered in drinking water to groups 6 through 10 using the same doses of each agent as in groups 1 through 4: group 5 (only L-NAME), group 6 (felodipine), group 7 (enalapril), and group 8 (felodipine plus enalapril). Groups 9 and 10 received L-NAME initially for 3 weeks followed by felodipine or felodipine plus enalapril, respectively, for the subsequent 3 weeks. All three treatments resulted in reductions in mean arterial pressure and total peripheral vascular resistance (P<.001) that were associated with important structural and functional renal microcirculatory improvements. Thus, the pathological nephrosclerosis (subcapsular and juxtamedullary) glomerular and arteriolar injury scores were improved (P<.05 at least) in association with normalization of afferent and efferent arteriolar resistances, and single-nephron glomerular filtration rate, plasma flow, and blood flow were significantly improved, as well as the ultrafiltration coefficient (compared with group 5, L-NAME). Thus, the calcium antagonist felodipine, alone or in combination with an ACE inhibitor, not only prevented but also reversed L-NAME-exacerbated hypertensive nephrosclerosis in SHR.

Animals↗
PubMed1998

Recent advances on large arteries in hypertension.

The most classic hemodynamic concept explaining the increased mean arterial pressure in hypertension reflects an increased total peripheral resistance dynamically and an increased wall-to-lumen ratio to suppress smaller arteries. However, a more current consideration takes into account not only that steady component but also the pulsatile component of blood pressure, a point that importantly modifies the traditional hemodynamic definition. Whereas mean arterial pressure is almost constant along the arterial tree, the pulse pressure increases markedly from the more central to the peripheral arteries, indicating that in vivo each artery should be characterized according to its own blood pressure curve. This important concept implies major modifications in the methods used to investigate the relationships between mechanical factors and large artery structure and function. It therefore seems reasonable that in hypertension the large arteries should no longer be considered as passive conduits but rather in terms of their active behavioral response to the mechanical forces to which they are subjected. New investigational aspects in hypertension therefore now involve not only genetic, cellular, and molecular mechanisms but also transductional hemodynamic mechanisms reflecting changing patterns in the extracellular matrix that influence structural remodeling of the vessels.

Animals↗
PubMed1997

Current clinical pathophysiologic considerations in essential hypertension.

Over the years, much has been learned from unraveling the pathophysiological alterations associated with the hypertensive diseases. Despite this large base of fundamental and clinical information, our knowledge continues to expand. This article discusses the multifactorial nature of hypertensive disease, including the vascular and cardiac participation in the elevation of arterial pressure and in target organ involvement by the disease. Some of the most exciting advances of the last decade are summarized in this review.

Adult↗
PubMed1997

Systemic and regional hemodynamic effects of gallopamil in patients with essential hypertension.

Systemic and regional hemodynamics were assessed in 10 patients with uncomplicated mild to moderate essential hypertension before and during gallopamil therapy. Cardiac output was measured in triplicate with indocyanine dye. Plasma volume and renal blood flow were measured radioisotopically. Immediately following the initial dose of a slow-release (SR) formulation of gallopamil, a significant fall in arterial pressure associated with a decreased total peripheral resistance and a reflex increase in heart rate and cardiac output were seen. Then, after 8-12 weeks of treatment, arterial pressure and total peripheral resistance remained reduced, but heart rate and cardiac output returned to pretreatment levels. Gallopamil also produced significant reductions in renal and splanchnic vascular resistance. Plasma volume and total blood volume did not change. Thus, gallopamil reduced arterial pressure and vascular resistances without fluid retention or prolonged reflexive changes.

Calcium Channel Blockers↗
PubMed1997

Disparate effects of ACE-inhibitors and calcium antagonists on left ventricular structure and function in essential hypertension.

The present study was designed to compare the effects of angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists-the two drug classes thought to be most effective in reducing left ventricular hypertrophy-on arterial pressure, left ventricular structure and function in patients with essential hypertension. After a placebo period of 4 weeks, a population of 96 patients were treated either with one of five different ACE inhibitors or one of six different calcium antagonists. Cardiac structure and function was assessed by 2D-guided M-mode echocardiography. Whereas both drug classes lowered arterial pressure to the same extent, ACE inhibitors had a more pronounced effect on posterior and septal wall thickness and left ventricular mass index than calcium antagonists. Diastolic function, as measured by peak filling rate and duration of rapid filling, improved in both treatment groups to the same extent. However, systolic performance, as assessed by midwall fractional fibre shortening, was significantly improved by ACE inhibitors only. Myocardial contractility (end-systolic wall stress/end-systolic volume index) showed no significant change in the ACE inhibitor group but decreased after treatment with calcium antagonists. We conclude that both calcium antagonists and ACE inhibitors lower arterial pressure and increase left ventricular filling to the same extent. However, compared with calcium antagonists, ACE inhibitors had a more pronounced effect on left ventricular mass and improved systolic ventricular performance in patients with essential hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

ACE inhibition reduces left ventricular mass independent of pressure without affecting coronary flow and flow reserve in spontaneously hypertensive rats.

Systemic and regional (including coronary) hemodynamics were studied in spontaneously hypertensive and normotensive Wistar Kyoto rats after 3 weeks of treatment with one of the three doses of the angiotensin converting enzyme inhibitor, ramipril. The effects of respective treatments on cardiovascular mass and systemic, coronary, and regional hemodynamics (at rest, during maximal treadmill exercise, and during dipyridamole infusion) then were evaluated in conscious rats using radiomicrosphere techniques. Low-dose ramipril (10 micrograms/kg/day by gavage) neither decreased arterial pressure nor reduced cardiac mass. However, medium (100 micrograms/kg/day) and high (1 mg/kg/day) doses reduced total cardiac and left ventricular masses to the same extent in spontaneously hypertensive rats, despite a much greater fall in arterial pressure with a high dose. Resting cardiac index, and myocardial and all other organ blood flows remained unchanged in both strains. When compared with Wistar Kyoto rats, coronary circulation was impaired in untreated spontaneously hypertensive rats (ie, reduced coronary flow and flow reserve and increased minimal coronary vascular resistance during dipyridamole infusion). This remained unchanged by ramipril. Furthermore, significant (and comparable) increases in cardiac index and myocardial blood flow and decreases in coronary vascular resistance were produced by maximal treadmill exercise in both strains. This also was unaffected by ramipril. These data showed that angiotensin converting enzyme inhibition with suboptimal and optimal hypotensive doses of ramipril reversed left ventricular hypertrophy in spontaneously hypertensive rats, but coronary flow, flow reserve, and minimal coronary vascular resistance remained unchanged despite left ventricular hypertrophy reversal.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Arthus C. Corcoran Memorial Lecture. Influence of nitric oxide and angiotensin II on renal involvement in hypertension.

Remarkable advances have been made with prolonged antihypertensive therapy in reversing cardiovascular morbidity and mortality. Deaths from stroke have been reduced by 70% and from coronary heart disease by 35%. In contrast, endstage renal disease resulting from hypertension continues to increase. The explanations for this seeming paradox remain unresolved even though experimental models have demonstrated that certain antihypertensive agents may have beneficial renal and intrarenal hemodynamic effects; but reversal of the intrarenal pathological lesions have not been shown to improve. This discussion summarizes recent studies from our laboratory in aged (73- and 85-week-old) spontaneously hypertensive rats (SHR) with naturally occurring end-stage renal disease and in a model of aged SHR employing nitric oxide inhibition in younger, adult (20-week-old) SHR. Our findings demonstrated that the systemic and whole renal hemodynamics, intrarenal glomerular dynamics, proteinuria, and renal pathological lesions can be prevented or reversed with angiotensin-converting enzyme inhibition therapy but not with hydrochlorothiazide (at similar levels of arterial pressure reduction). The implications and possible mechanisms involved in the development of both naturally occurring and nitric oxide-exacerbated SHR are multifactorial, involving the endothelial nitric oxide system and its interaction with angiotensin II (and possibly bradykinin) among other factors. Moreover, these pathophysiological cellular mechanisms may be shared by the aging process as well as in naturally occurring spontaneous hypertension in the rat and, perhaps, in humans with essential hypertension. Thus, antihypertensive therapy seems to be specific in its ability to prevent and even reverse the pathophysiological derangements of renal involvement in hypertension. Thus, prevention and reversal of end-stage renal disease do not seem to require greater reduction of arterial pressure than with other target-organ involvement. However, they do require specific inhibition of the arteriolar and glomerular lesions produced by the disease.

Aging↗
PubMed1997

Enalapril and losartan reduced cardiac mass and improved coronary hemodynamics in SHR.

Among the multiple mechanisms postulated for the increased risk of hypertensive left ventricular hypertrophy (LVH), coronary hemodynamic alterations remain a strong possibility. This study was designed to compare the effects of treatment with an ACE inhibitor (enalapril) and an angiotensin AT1 receptor antagonist (losartan) on systemic and coronary hemodynamics and to determine whether the combination of these two renin-angiotensin system (RAS) inhibitor would be as or more effective in reducing mean arterial pressure (MAP), left ventricular (LV) mass, and improving coronary hemodynamics than either regimen alone. Thus, 23 week old spontaneously hypertensive rats (SHR) were treated (12 weeks) with tap water (C), enalapril (30 mg.kg-1.d-1), losartan (30 mg.kg-1.d-1), or their combination (15 mg.kg-1.d-1). Age-matched Wistar-Kyoto (WKY) rats served as normotensive controls. After 12 weeks, systemic and coronary hemodynamics were determined (15 microns radiolabeled microspheres) at baseline, during maximal treadmill exercise, and during maximal dilation (dipyridamole). Enalapril and losartan equally reduced MAP and LV mass in association with a decreased total peripheral resistance. The RAS combination reduced MAP and LV mass more than either drug alone. Resting cardiac index and coronary blood flow (CBF) per unit of LV mass did not differ among the groups. Although enalapril did not improve coronary flow reserve (CFR), it diminished minimal coronary vascular resistance (MCVR); losartan improved both. However, the combination was more effective than either agent alone, reaching values close to normotensive WKY controls. In conclusion, these data demonstrated significantly impaired maximal CBF, CFR, and MCVR in untreated SHR, but losartan alone and in combination with enalapril improved systemic and coronary hemodynamics more than enalapril alone.

Angiotensin Receptor Antagonists↗