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

Abstract

Left ventricular remodeling in hypertension is associated with cardiac interstitial and perivascular collagen deposition. The dual angiotensin I converting enzyme/neutral endopeptidase inhibitor omapatrilat (also called vasopeptidase inhibitor) improves left ventricular remodeling in experimental heart failure. We hypothesized that omapatrilat would induce regression of cardiac and vascular fibrosis in hypertension. We, therefore, investigated the effect of omapatrilat on collagen deposition in heart and aorta of stroke-prone spontaneously hypertensive rats (SHRSP). Twenty-week-old normotensive Wistar-Kyoto (WKY) rats, untreated SHRSP, and SHRSP treated with omapatrilat (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. After 10 weeks, systolic blood pressure (BP) was significantly ( P < .01) reduced in omapatrilat-treated versus untreated SHRSP. Interstitial collagen density was significantly decreased in the subendocardial myocardium (to 2.71 ± 0.24% v 4.12 ± 0.30%, respectively, P < .05) and in the mid-myocardium of omapatrilat-treated versus untreated SHRSP (to 3.01 ± 0.25 v 4.19 ± 0.17% respectively, P < .05). Perivascular collagen was significantly ( P < .05) decreased in the subepicardial, mid-myocardial and, subendocardial regions of the myocardium of omapatrilat-treated versus untreated SHRSP. Aortic collagen content decreased in omapatrilat-treated versus untreated SHRSP (to 36.1 ± 2.8 v 58.8 ± 6.1 × 10 3μm 2/mm section, respectively, P < .05). In conclusion, in addition to being a potent antihypertensive agent, omapatrilat significantly improves cardiac and vascular fibrosis in SHRSP.