Isolated Systolic Hypertension in Elderly WKY Is Reversed With l -Arginine and ACE Inhibition

Abstract

This study was designed to examine the preventability of progressive deterioration of cardiovascular structure and function in very old Wistar-Kyoto (WKY) rats with isolated systolic hypertension (ISH). To this end, male 18-month-old normotensive WKY rats were given either placebo or l -arginine (70 mg · kg −1 · d −1 ) and an ACE inhibitor (enalapril, 30 mg · kg −1 · d −1 ) for 6 months. These control and treated rats were studied at the age of 2 years by examining: cardiovascular mass and collagen content, cardiac function, and systemic and regional (including coronary) hemodynamics. Additional data obtained in adult, 35-week-old WKY are included for comparison. ISH associated with increased total peripheral resistance was found in the old, untreated WKY, and this was prevented by the combined treatment. The untreated rats also exhibited impaired left ventricular function, as denoted by increased left ventricular end-diastolic pressure and reduced maximal rates of rise and fall of left ventricular pressure. These functional changes were also ameliorated with the combined treatment. Coronary hemodynamics were also compromised in the untreated WKY; and therapy improved coronary flow reserve and minimal coronary vascular resistance in both ventricles of the old WKY in parallel with reduction of arterial pressure. Blood flow to various other organs was uncompromised in the old rats, although increased vascular resistances were observed in untreated old WKY with ISH. These changes were also improved by the combined therapy. Finally, therapy diminished left ventricular mass and collagen concentration in old WKY compared with the untreated WKY. However, when compared with the 35-week-old WKY, both groups of old WKY (untreated and treated) demonstrated myocardial fibrosis, depressed ventricular function, and compromised coronary hemodynamics. Therefore, l -arginine and ACE inhibitory therapy ameliorated the hypertensive and associated adverse cardiovascular changes in old WKY, although it failed to improve totally the progressive deterioration of cardiovascular structure and function that occurred with aging. The results suggest that different mechanisms may be responsible for the hypertension- and age-related cardiovascular changes, although they may appear to be similar.