Prolonged L-Arginine on Cardiovascular Mass and Myocardial Hemodynamics and Collagen in Aged Spontaneously Hypertensive Rats and Normal Rats

Abstract

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)...

Ischemia and fibrosis: the risk mechanisms of hypertensive heart disease

“…We have also observed similar decreases in arterial pressure, total peripheral resistance, LV mass and collagen following prolonged L-arginine treatment, although RV collagen was not as decreased (39). These LV structural and functional improvements with L-arginine were observed only in SHR, suggesting that these endothelial dysfunctional changes in response to L-arginine were more related to hypertension than to aging.…”

“…These findings support the concept that local endothelial production of nitric oxide synthesis and endothelial dysfunction of the coronary circulation are thereby augmented. In addition, we have also reported that L-arginine administration also improves intracoronary hemodynamics and other pathophysiological alterations induced by hypertensive coronary vascular disease (39). Moreover, recent clinical studies have also shown that prolonged L-arginine treatment of patients with hypertensive or atherosclerotic vascular disease improves the associated clinical and hemodynamic alterations (40).…”

Ethnicity-specific differences in L-arginine status in South African men

“…19 L-arginine supplementation improves the reduced vasodilatory response in offspring of hypertensive patients and in normotensive patients with familial essential hypertensive histories, suggesting that a genetic predisposition to essential hypertension involves a defect in NO generation. 9 Various aspects of the effect of L-arginine augmentation have been studied in human subjects, 20 --22 in animal experiments 23,24 and in tissue culture. 25 However, there is a dearth of epidemiological studies investigating ethnic differences in L-arginine utilisation.…”

Upregulation of Vascular Arginase in Hypertension Decreases Nitric Oxide–Mediated Dilation of Coronary Arterioles

“…1 Mounting evidence suggests that this vascular impairment may be related to a diminished production and bioavailability of the potent vasodilator nitric oxide (NO), which may result from an increased vascular production of superoxide anion 2 or decreased endothelial levels of tetrahydrobiopterin 3,4 or L-arginine. 5 Interestingly, administration of NO precursor L-arginine restores endothelium-mediated vasodilatory function in patients with essential hypertension, 5 improves coronary hemodynamics in spontaneously hypertensive rats, 6 and increases NO production and reduces blood pressure in hypertensive rats with 7 or without 8 renal failure. These results suggest the possible reduction of L-arginine availability for NO synthesis in hypertension.…”