Abstract-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 ⅐ kg, and group 4 (felodipine plus enalapril, 15 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 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 (PϽ.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 (PϽ.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. (Hypertension. 1998;31:795-801.)

Abstract-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. Key Words: hypertension Ⅲ aging Ⅲ mass, ventricular Ⅲ mass, aortic Ⅲ hemodynamics, coronary Ⅲ myocardial collagen concentration Ⅲ L-arginine M orphological and functional changes that occur in the cardiovascular system with hypertension and aging are similar in many respects. 1-4 They include impaired cardiac performance and coronary hemodynamics and ventricular fibrosis. [5][6][7][8][9] In a recent study involving normotensive and spontaneously hypertensive rats (SHRs), aged 22, 35 and 65 weeks, we demonstrated that associated with aging per se there were progressive impairments in coronary hemodynamics with increased myocardial collagen deposition in both strains. 9 These changes were more pronounced in hypertensive rats at any age, as if hypertension might have induced premature aging alterations of cardiovascular system.Much evidence exists that suggests that the endothelium, in autocrine/paracrine and endocrine manners, participates in regulating cardiovascular structure and function. 10 The endothelial cells produce and release a variety of vasoactive substances, including nitric oxide (NO). 10 NO is a powerful vasodilator which is derived from L-arginine by the action of NO synthase. 11 Many reports have demonstrated that endothelial dysfunction of NO synthesis and release is present, or even precedes cardiovascular changes associated with hypertension and aging. [12][13][14][15][16][17][18][19] Thus, endothelial dysfunction may participate the development of hypertension and age-related changes in the coronary vasculature and myocardium. Therefore, the purpose of this study was to examine whether prolonged L-arginine administration, the initiator of NO production, could modulate cardiac fibrosis and deterioration of coronary hemodynamics in both old and hypertensive rats. To differentiate between hypertension-and age-induced changes, the results obtained in aging normotensive WistarKyoto rats (WKYs)...

Arterial hypertension is a global public health problem owing to its high prevalence and association with increased risk for cerebral, cardiac and renal events. Hypertension frequently clusters with other cardiometabolic risk factors, such as dysglycemia, low levels of high-density lipoprotein cholesterol and high triglyceride levels. These, along with other factors such as central obesity, increased inflammation, endothelial dysfunction and thrombosis, are components of the metabolic syndrome. All guidelines recommend that the first-line therapy in metabolic syndrome should be based on lifestyle modification, consisting of diet and moderate exercise for at least 30 min/day. Concerning drug treatment of hypertension associated with other cardiometabolic risk factors, many results of head-to-head studies have demonstrated a reduction in new-onset Type 2 diabetes in hypertensive patients treated with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, when compared with conventional antihypertensive therapy. The explanations of the different actions of both these drugs include several mechanisms related to pancreatic insulin release and insulin sensitivity improvement. Another mechanism by which the inhibition of the renin-angiotensin system may improve insulin sensitivity is through the partial peroxisome proliferator-activated receptor-gamma agonism of telmisartan. For that reason, telmisartan has been considered by some experts to be an antihypertensive agent that is particularly useful in the treatment of hypertension associated with cardiometabolic risk factors. The impact of the promising metabolic action exhibited by telmisartan on the outcome of hypertensive patients aggregating other cardiometabolic risk factors waits for adequately randomized and powered clinical trials.

Postinfarction ventricular septal defect is a life-threatening disorder that may be adequately treated if the diagnosis is obtained promptly. Two-dimensional color Doppler echocardiography is a reliable tool for this diagnosis and gives additional information regarding its location, size, and shape. The authors emphasize the feasibility of this method to depict a particular form of postinfarction interventricular septal rupture, which developed an aneurysm inside the right ventricular cavity. Its characteristics were completely defined by color Doppler echocardiography and confirmed at surgery. (ECHOCARDIOGRAPHY, Volume 13, May 1996)