Effect of Vasopeptidase Inhibition on Myocardial and Vascular Collagen in Stroke Prone Spontaneously Hypertensive Rats.
Left ventricular remodeling in hypertension is associated with cardiac interstitial and perivascular collagen deposition. The vasopeptidase inhibitor omapatrilat improves left ventricular remodeling in experimental heart failure. We hypothesized that omapatrilat would induce a regression of ventricular and vascular fibrosis in hypertension. We therefore investigated the effect of vasopeptidase inhibition on collagen deposition in heart and aorta of stroke prone spontaneously hypertensive rats (SHRSP). Ten-week old SHRSP were treated orally for 10 weeks with omapatrilat (40mg/kg/d). Collagen fibers in heart and descending thoracic aorta were stained with Sirius red. Collagen density was defined as the ratio of the area stained by Sirius red to the area of the studied field. After 10 weeks, systolic blood pressure was significantly (P<0.01) reduced in omapatrilat-treated vs untreated SHRSP. Collagen density was significantly decreased in the subendocardial myocardium of omapatrilat-treated vs untreated SHRSP (to 3.55 vs 7.53%, respectively, P<0.05) and in mid-myocardium (to 4.38 vs 7.92% respectively, P<0.01). Aortic collagen content decreased in omapatrilat-treated vs untreated SHRSP (to 22.7 vs 46.3×103μm/mm section, respectively, P<0.05). In conclusion, in addition to being a potent anti-hypertensive agent, omapatrilat significantly improves ventricular and arterial structure in SHRSP with regression of collagen deposition.