Isoproterenol-induced cardiac hypertrophy: role of circulatory versus cardiac renin-angiotensin system

Abstract

To assess the possible contribution of the circulatory and cardiac renin-angiotensin system (RAS) to the cardiac hypertrophy induced by a beta-agonist, the present study evaluated the effects of isoproterenol, alone or combined with an angiotensin I-converting enzyme inhibitor or AT(1) receptor blocker, on plasma and LV renin activity, ANG I, and ANG II, as well as left ventricular (LV) and right ventricular (RV) weight. Male Wistar rats received isoproterenol by osmotic minipump subcutaneously and quinapril or losartan once daily by gavage. Plasma and LV ANGs were measured by radioimmunoassay after separation by HPLC. Isoproterenol alone decreased blood pressure, more markedly when combined with losartan or quinapril. Isoproterenol significantly increased LV and RV weight and total collagen. Neither losartan nor quinapril inhibited the increases in LV or RV weight. Losartan prevented the increase in RV collagen but enhanced the increase in LV collagen. Isoproterenol increased plasma renin, ANG I, and ANG II three- to fourfold. Isoproterenol combined with losartan or quinapril, caused marked further increases except for a significant decrease in plasma ANG II with quinapril. Isoproterenol alone did not increase LV ANG II and, combined with losartan or quinapril, actually decreased LV ANG II. These results indicate that isoproterenol-induced cardiac hypertrophy is associated with clear increases in plasma ANG II, but not in LV ANG II. Both losartan and quinapril lower LV ANG II below control levels, but do not prevent the isoproterenol-induced cardiac hypertrophy. These findings do not support a role for the circulatory or cardiac RAS in the cardiac trophic responses to beta-receptor stimulation.

Effects of Captopril and Telmisartan on Matrix Metalloproteinase-2 and -9 Expressions and Development of Left Ventricular Fibrosis Induced by Isoprenaline in Rats

“…This feature is consistent with the previous reports. [6][7][8]10,14,17) In the present study, telmisartan had no influence on the isoprenalineinduced myocardial fibrosis. Leenen et al reported that losartan increased the isoprenaline-induced LV fibrosis.…”

Activation of brain renin-angiotensin-aldosterone system by central sodium in Wistar rats

“…As described previously (27), plasma ANG II concentration was measured by RIA after extraction on C18 Sep-Pak cartridges and separation by HPLC, and PRA was determined by RIA to measure the ANG I generated during incubation at 37°C for 1 h.…”

Gq-Coupled Receptor Agonists Mediate Cardiac Hypertrophy Via the Vasculature

“…Surprisingly, ISO treatment induced an increase in blood pressure ( Figure 4B), although this has been shown previously with catecholamine administration. 3,14 The substantial increase in heart rate elicited by chronic treatment with this Gs-coupled receptor agonist (untreated mice, 242Ϯ22 bpm; ISO-treated mice, 577Ϯ29 bpm) likely mediates a mechanical mechanism to increase blood pressure and override the vasodilatory signals of the ligand. The hyperten- …”

“…Additionally, ISO administration, which acts via the Gs-coupled ␤AR, has been shown to activate the Gq-coupled circulatory renin-angiotensin system. 14 To delineate the contribution of Gq signaling in the vasculature and heart to the development of cardiac hypertrophy, after exposure to Gq-coupled receptor agonists, we have developed a line of transgenic mice that express the GqI exclusively in VSM cells under the control of the SM22␣ promoter. Herein, we describe the physiological implications of inhibiting Gq-signal transduction specifically in either the vasculature or myocardium, and determine its impact on blood pressure and cardiac hypertrophy.…”