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Biomedical subjects

E D Frohlich

Publications and source records attributed to E D Frohlich.

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

Hypertension and the heart.

Sustained increase in arterial pressure causes left ventricular hypertrophy and adversely affects all myocardial compartments: myocytes, interstitium, and coronary vasculature. Ventricular hypertrophy significantly increases the risk for cardiovascular morbidity and mortality in hypertensive disease. Impairments in coronary circulation and ventricular fibrosis, which are an essential part of hypertensive disease, contribute to that increased risk. This report discusses the mechanisms of hypertension-induced myocardial collagen accumulation and impairments in coronary hemodynamics. Particular attention is given to the interaction of hypertension and aging because aging aggravates hypertensive changes and the incidence of hypertension increases with aging. The effect of therapy on hypertension-induced ventricular fibrosis and impairment in coronary hemodynamics and the risk associated with these changes are also discussed.

Aging↗
PubMed2000

AT1 receptors: coronary flow and flow reserve.

Angiotensin II, through its effects at the angiotensin-type 1 receptor, elevates arterial pressure and exacerbates hypertensive heart disease. Alterations in coronary hemodynamics, including reductions in coronary blood flow and flow reserve promotes coronary insufficiency and contributes to the increased cardiovascular risk associated with these conditions. In spontaneously hypertensive rats, coronary flow reserve, the difference between basal coronary blood flow and the flow achieved during maximal coronary vasodilation achieved by dipyridimole, was increased to a greater extent after treatment for 3 months with an angiotensin II receptor blocker as compared with an angiotensin converting enzyme inhibitor. The combination of the two agents, in equidepressor doses, almost restored coronary flow reserve to levels seen in normotensive Wistar Kyoto rats. This finding suggests a possible advantage of combination angiotensin converting enzyme inhibitors and angiotensin II receptor blocker therapy in patients with hypertension and hypertensive heart disease.

Animals↗
PubMed2000

Department of Veterans Affairs hypertension meeting : a proposal for improved care.

A major invitational hypertension meeting was hosted by the Department of Veterans Affairs (VA) in Washington, DC, on May 26 to 28, 1999. It followed a report that only 25% of hypertensive veterans had adequate levels of treated blood pressure and focused on how control of hypertension could be improved both immediately and in the future. After the presentation of brief outlines of 5 unresolved basic science questions, 2 general topics were considered: (1) 30 years of change in hypertension and its treatment and (2) current healthcare delivery mechanisms and how to improve them. Since 1970, the severity of hypertension has decreased, malignant hypertension has disappeared, and the prognostic roles of systolic and diastolic blood pressure have been reversed as hypertension became milder. Five VA Cooperative Studies have provided important data: the 1970 Freis Trial report demonstrated the value of treatment, 2 trials showed that some controlled patients can decrease or even discontinue pharmacological treatment without recrudescent hypertension, a blinded trial was performed on the efficacy of different antihypertensive drugs, and an unblinded trial showed that diuretics and beta-blockers are the most effective agents when caregivers choose the agent and dose. Two healthcare models were considered: (1) the patient-friendly VA Hypertension Screening and Treatment Program that was introduced in 1972, which controls 80% of patients at the goal of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure with diuretics and keeps patients in the program an average of 7.5 years, and (2) the newer primary care health maintenance organization-like model in the VA and throughout the United States. Choosing a regimen and monitoring control of blood pressure and compliance with therapy were discussed. The meeting was closed with 6 general recommendations for improving the care of hypertensive patients.

Antihypertensive Agents↗
PubMed2000

Ischemia and fibrosis: the risk mechanisms of hypertensive heart disease.

Mechanisms underlying risk associated with hypertensive heart disease (HHD) and left ventricular hypertrophy (LVH) are discussed in this report and provide a rationale for understanding this very common and important cause of death from hypertension and its complications. Emphasized are impaired coronary hemodynamics, endothelial dysfunction, and ventricular fibrosis from increased collagen deposition intramurally and perivascularly. Each is exacerbated by aging and, perhaps, also by increased dietary salt intake. These functional and structural changes promote further endothelial dysfunction, altered coronary hemodynamics, and diastolic as well as systolic ventricular contractile function in HHD. The clinical endpoints of HHD include angina pectoris (with or without atherosclerosis of the epicardial coronary arteries), myocardial infarction, cardiac failure, lethal dysrhythmias, and sudden death. The major concept to be derived from these alterations is that not all that is clinically recognized as LVH is true myocytic hypertrophy and structural remodeling. Other major co-morbid changes occur that serve to increase cardiovascular risk including impaired coronary hemodynamics, endothelial dysfunction, and ventricular fibrosis.

Animals↗
PubMed1999

The necessity for recognition and treatment of patients with "mild" hypertension.

A dramatic evolution has occurred in the past four decades in our underlying knowledge of pathophysiology of the hypertensive diseases and in the availability of myriad pharmacologic agents for control of hypertension. This report provides a current review of antihypertensive treatment interspersed with personal opinions supported by appropriate references. It focuses on the recent national recommendations dealing with the prevention, detection, evaluation and treatment of the disease (JNC-6). Whereas I believe that the height of arterial pressure is of primary importance, it is not the sine qua non explaining all target organ involvement or complications of hypertensive disease. Consequently, all that is classified today as Stages 1 and 2 hypertension (old terminology: "mild" and "moderate") in terms of blood pressure elevation does not explain all outcomes of disease. Indeed, JNC-6 introduced the new concept of risk stratification for therapy based not only on the height of systolic and diastolic pressure but also on the presence of target organ involvement, comorbidity and other risk factors. However, after considerable advances since the inception of the National High Blood Pressure Education Program (NHBPEP) in 1972, it appears that we are avoiding our responsibilities and reversing our gains. It is of vital importance that we renew our efforts to identify, evaluate and treat all patients with hypertension; this is especially so for the vast numbers of patients with Stages 1 and 2 hypertension.

Antihypertensive Agents↗
PubMed1999

L-arginine reverses severe nephrosclerosis in aged spontaneously hypertensive rats.

OBJECTIVE: Acute and prolonged effects of L-arginine on systemic and renal hemodynamics and on renal pathological changes were examined in 85-week-old spontaneously hypertensive rats (SHR). RESULTS: After 3 weeks of L-arginine administration (n = 9; 2 g/l in drinking water), mean arterial pressure remained unchanged, although the cardiac index increased (187 +/- 26 versus 263 +/- 15 ml/min per kg; P < 0.05) and total peripheral resistance decreased (1.15 +/- 0.18 versus 0.67 +/- 0.06 AU; P < 0.05); the glomerular filtration rate increased (0.41 +/- 0.07 versus 0.79 +/- 0.07 ml/min; P < 0.01). Control untreated, aged SHR (n = 10) demonstrated severe nephrosclerosis histologically, but those treated with L-arginine demonstrated a markedly reduced glomerular injury score (164 +/- 22 versus 83 +/- 9; P < 0.005), and their urinary protein excretion (39 +/- 5 versus 19 +/- 5 mg/100 g body weight per day; P < 0.05) and serum creatinine concentration (1.4 +/- 0.1 versus 0.9 +/- 0.1 mg/dl; P < 0.05) diminished. Intravenous L-arginine (300 mg/kg body weight) given to untreated SHR reduced mean arterial pressure, increased the cardiac index (+98 versus +1%; P < 0.05) and decreased total peripheral resistance (+56 versus +13%, P < 0.005); however, these variables remained unchanged after 3 weeks of L-arginine treatment. CONCLUSIONS: Three weeks of treatment with L-arginine improved systemic hemodynamics, renal function and renal histologic changes in aged SHR with naturally occurring nephrosclerosis. These data provide an important insight into the pathophysiology of nephrosclerosis in hypertension and with aging, which is seen clinically.

Animals↗
PubMed1999

Pharmacologic agents on cardiovascular mass, coronary dynamics and collagen in aged spontaneously hypertensive rats.

OBJECTIVE: To determine whether antihypertensive treatment could alter hypertension and age-related progressive impairment of coronary hemodynamics and cardiac fibrosis in aged spontaneously hypertensive rats (SHR). DESIGN: Old SHR were given their respective therapy for 3 months. To differentiate between hypertension and age-related changes, a comparison was made between left and right ventricular indices since the right ventricle was not exposed to pressure overload. METHODS: Male, 65-week-old spontaneously SHR were divided into three groups and were given either vehicle, felodipine (30 mg/kg per day) or enalapril (30 mg/kg per day). After 12 weeks of the respective treatments, systemic and coronary hemodynamics (radionuclide-labelled microspheres), right and left ventricular and aortic mass indices, and right and left ventricular hydroxyproline concentrations (an estimate of collagen) were determined. RESULTS: Arterial pressure and total peripheral resistance were reduced to the same extent in SHRs treated with either felodipine or enalapril; however, compared to the control rats, enalapril was more effective in reducing left ventricular and aortic mass indices. Both agents also improved coronary hemodynamics of both ventricles in aged SHR but enalapril was more effective as indicated by a greater increase in coronary flow reserve and a greater decrease in minimal coronary vascular resistance. Furthermore, enalapril but not felodipine reduced left ventricular hydroxyproline concentration; and right ventricular hydroxyproline concentration increased with felodipine but remained unchanged with enalapril. CONCLUSIONS: Both enalapril and felodipine ameliorated adverse cardiovascular effects of hypertension in the aged SHRs within 12 weeks, as demonstrated by reduced arterial pressure, diminished left ventricular mass, and improved coronary hemodynamics. Enalapril also decreased aortic mass and left ventricular collagen concentration and appeared to be more effective in improving coronary hemodynamics than felodipine, possibly as a result, in part, of reduced myocardial fibrosis.

Aging↗
PubMed1999

Prolonged L-arginine on cardiovascular mass and myocardial hemodynamics and collagen in aged spontaneously hypertensive rats and normal rats.

This study was designed to examine whether L-arginine could prevent hypertension- and age-related impairment of coronary hemodynamics and cardiac fibrosis in aged (80-week-old) rats. To differentiate between hypertension- and age-related changes, the study was performed in both normotensive Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHR). Male 1-year-old rats of both strains were divided into 2 groups and given either placebo or L-arginine (1.2 g/L) in drinking water. After 6 months, systemic and coronary hemodynamics (radionuclide-labeled microspheres), right and left ventricular and aortic mass indexes, and ventricular hydroxyproline (an estimate of collagen) concentrations were determined. In the aged WKYs, L-arginine did not affect any of the examined variables except slightly reducing total peripheral resistance. In contrast, L-arginine diminished arterial pressure, total peripheral resistance, and left ventricular and aortic mass indexes in the SHRs; it also increased coronary flow reserve and reduced minimal coronary flow resistance and myocardial hydroxyproline concentration. These findings demonstrated that L-arginine ameliorated adverse cardiovascular effects of hypertension in aged SHRs, as demonstrated by reduced arterial pressure and total peripheral resistance, diminished left ventricular mass and collagen content, and improved coronary hemodynamics. There were no important effects in the old WKYs.

Aging↗
PubMed1999

Differential effects of T- and L-type calcium antagonists on glomerular dynamics in spontaneously hypertensive rats.

To determine whether there is a difference in the effects of T- and L-type calcium antagonists on systemic, renal, and glomerular hemodynamics, the pathological changes of N(G)-nitro-L-arginine methyl ester (L-NAME)-exacerbated nephrosclerosis and clinical alterations were investigated in spontaneously hypertensive rats (SHR). Seven groups of 17-week-old male SHRs were studied: Group 1, control; Group 2, mibefradil, 50 mg. kg(-1). d(-1); Group 3, L-NAME in drinking water, 50 mg/L; Group 4, L-NAME (50 mg/L) plus mibefradil (50 mg. kg(-1). d(-1)); Group 5, L-NAME (50 mg/L) plus amlodipine (10 mg. kg(-1). d(-1)); Group 6 and 7, L-NAME (50 mg/L) for 3 weeks followed by mibefradil (50 mg. kg(-1). d(-1)) or amlodipine (10 mg. kg(-1). d(-1)), respectively, for the subsequent 3 weeks. Both the T- and L-channel calcium antagonists similarly reduced mean arterial pressure and total peripheral resistance index. These changes were associated with significant decreases in afferent and efferent glomerular arteriolar resistances and the ultrafiltration coefficient (P<0.01). Furthermore, the histopathological glomerular and arterial injury scores and urinary protein excretion were also significantly improved (P<0.01), and left ventricular and aortic masses were significantly diminished in all treated groups. Both drugs, mibefradil and amlodipine, had effects of increasing the single-nephron glomerular filtration ratio (SNGFR), and single-nephron plasma flow (SNPF), and of reducing glomerular afferent arteriolar resistance and urinary protein excretion. Thus, the T-type (mibefradil) and L-type (amlodipine) calcium antagonists each prevented and reversed the pathophysiological alterations of L-NAME-exacerbated hypertensive nephrosclerosis in SHR. The T-type calcium antagonist (mibefradil) seemed to have been more effective than the L-type amlodipine antagonist and it produced a greater reduction in afferent arteriolar resistance while preserving SNGFR.

Amlodipine↗
PubMed1999

Apoptosis, coronary arterial remodeling, and myocardial infarction after nitric oxide inhibition in SHR.

This study was designed to investigate the relationship between apoptosis (programmed cell death) and coronary arterial remodeling in spontaneously hypertensive rats (SHR) following prolonged nitric oxide synthesis inhibition. In addition, we evaluated whether the development of coronary arterial smooth muscular cell apoptosis was related to hemodynamics or to vascular hypertrophy. Three groups of 20-week-old male SHR were investigated: controls, and two groups that received two doses of N(G)-nitro-L arginine (L-NAME, 50 mg/L and 80 mg/L) each for 3 weeks. Mean arterial pressure and total peripheral resistance index increased whereas cardiac index diminished with L-NAME. Pathohistological study demonstrated increased pericardiac fibrosis and coronary arterial injury score in the L-NAME group in a dose-dependent manner. The high dose of L-NAME (Group 3) produced myocardial infarction in 78% of the rats. The wall:lumen ratio of epicardial coronary arteries was greater in L-NAME treated SHR (0.23+/-0.02 versus 0.16+/-0.02; P<0.05) and was associated with markedly increased apoptosis (15.3+/-6 versus 1. 9+/-1; P<0.05) without smooth muscle cell proliferation (PCNA positive cells). Apoptosis occurred predominantly in hypertrophic coronary arterial smooth muscular cells; myocardial infarction and ventricular fibrosis were exacerbated by impaired hemodynamics induced by L-NAME. These data suggest that coronary endothelial dysfunction and myocardial ischemic disease induced by L-NAME were responsible for apoptosis of coronary arterial smooth muscle cells, myocardial fibrosis, and infarction, all pathological findings that are consistent with what may be found in clinical hypertensive heart disease.

Animals↗