Effect of ACE/NEP inhibition on cardiac and vascular collagen in stroke-prone spontaneously hypertensive rats

Left ventricular remodeling in hypertension is associated with cardiac inte rstitial and perivascular collagen deposition. The dual angiotensin I conve rting enzyme/neutral endopeptidase inhibitor omapatrilat (also called vasop eptidase inhibitor) improves left ventricular remodeling in experimental he art failure. We hypothesized that omapatrilat would induce regression of ca rdiac and vascular fibrosis in hypertension. We, therefore, investigated th e effect of omapatrilat on collagen deposition in heart and aorta of stroke -prone spontaneously hypertensive rats (SHRSP). Twenty-week-old normotensiv e Wistar-Kyoto (WKY) rats, untreated SHRSP, and SHRSP treated with omapatri lat (40 mg/kg per day, orally) for 10 weeks were investigated. Collagen in the heart and the descending thoracic aorta was stained with Sirius red. Af ter 10 weeks, systolic blood pressure (BP) was significantly (P < .01) redu ced in omapatrilat-treated versus untreated SHRSP. Interstitial collagen de nsity was significantly decreased in the subendocardial myocardium. (to 2.7 1 <plus/minus> 0.24% v 4.12 +/- 0.30%, respectively, P < .05) and in the mi d-myocardium of omapatrilat-treated versus untreated SHRSP (to 3.01 <plus/m inus> 0.25 v 4.19 +/- 0.17% respectively, P < .05). Perivascular collagen w as significantly (P < .05) decreased in the subepicardial, mid-myocardial a nd, subendocardial regions of the myocardium of omapatrilat-treated versus untreated SHRSP. Aortic collagen content decreased in omapatrilat-treated v ersus untreated SHRSP (to 36.1 +/- 2.8 v 58.8 +/- 6.1 x 10(3) mum(2)/mm Sec tion, respectively, P < .05). In conclusion, in addition to being a potent antihypertensive agent, omapatrilat significantly improves cardiac and vasc ular fibrosis in SHRSP. Am J Hypertens 2001;14:1067-1072 (C) 2001 American Journal of Hypertension, Ltd.