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Biomedical subjects

L Sherry

Publications and source records attributed to L Sherry.

5 recordsLinked to original sources
PubMed2000

Regulation of the myocardial endothelin system by angiotensin-II and losartan.

Evidence for interactions between the endothelin (ET) and renin-angiotensin systems is plentiful in vitro, but few studies have investigated these interactions in vivo. In the study reported here, we have investigated the influence of chronic angiotensin-II (A-II) infusion in vivo on expression of preproendothelin-1 (PPET-1) and endothelin-A- (ET(A)) and endothelin-B- (ET(B)) receptor mRNA in the heart. The role of the angiotensin type 1 (AT1)-receptor in mediating the actions of A-II was studied using losartan, the selective AT1-receptor antagonist. Male rats received an infusion of A-II (200 ng/kg/min) or vehicle for 14 days via mini-osmotic pumps; losartan (10 mg/kg/day) was administered in the drinking water. PPET-1 and ET(A)- and ET(B)-receptor mRNA were detected in heart sections using nonradioactive antisense in situ hybridization. Independent treatments with either A-II or losartan had no significant effect on PPET-1, ET(A)- or ET(B)-receptor expression. Combined treatment resulted in an increase in PPET-1 mRNA (p < 0.001) and ET(B)-receptor mRNA expression (p < 0.01), while ET(A)-receptor mRNA expression was decreased (p < 0.001). These results suggest that selective AT1-receptor blockade, in the presence of an elevated plasma A-II concentration, causes upregulation of ET-1 synthesis in the myocardium as well as modification of ET receptor expression. These effects may be mediated via angiotensin type 2 (AT2)-receptors.

Aldosterone↗
PubMed1998

Differential effects of angiotensin II on cardiac cell proliferation and intramyocardial perivascular fibrosis in vivo.

BACKGROUND: Growth effects of angiotensin II (Ang II) contribute to cardiac remodeling. Remodeling, in turn, may be influenced by proliferation of nonmyocytes. The aims of this study were to determine in vivo which cardiac cell types proliferate in response to Ang II, to evaluate whether proliferation is mediated by the Ang II AT1 receptor, and to establish whether blood pressure affects cell proliferation by comparing proliferation in the normotensive right atrium and ventricle and pressure-overloaded left ventricle. METHODS AND RESULTS: Groups of 8 Wistar rats were implanted with miniosmotic pumps releasing 5-bromo-2'-deoxyuridine (BrdU) as a cell proliferation marker for 2 weeks. Two groups received Ang II infusions via a second minipump and drinking water+/-losartan. Two groups received vehicle+/-losartan. Cell proliferation was assessed as the percentage of nuclei that incorporated BrdU. Ang II increased proliferation within medial vascular smooth muscle cells (VSMCs) and in associated adventitial/interstitial fibroblasts of intramyocardial coronary arterioles but decreased proliferation of myoendothelial cells. Despite increased blood pressure, proliferation in atria and ventricles was similar. Aldosterone levels were not significantly elevated, suggesting direct proliferative effects of Ang II. Losartan reduced Ang II-induced VSMC and adventitial fibroblast proliferation but had no effect on myoendothelial cell proliferation. CONCLUSIONS: These results indicate direct, differential effects of Ang II on proliferation of atrial and ventricular nonmyocytes. VSMC and fibroblast proliferation is AT1 receptor-dependent, whereas myoendothelial cells are controlled by an AT1-independent mechanism. The effects are independent of aldosterone and blood pressure and have important implications in renin-dependent hypertension and chronic cardiac failure when circulating Ang II is elevated.

Aldosterone↗