Essential Role for Vascular Gelatinase Activity in Relaxin-Induced Renal Vasodilation, Hyperfiltration, and Reduced Myogenic Reactivity of Small Arteries

摘要: During pregnancy, relaxin stimulates nitric oxide (NO)–dependent renal vasodilation, hyperfiltration and reduced myogenic reactivity of small arteries via the endothelial ETB receptor subtype. Our objective in this study was to elucidate mechanisms by which receptor/NO vasodilatory pathway. Using chronically instrumented conscious rats, we demonstrated that a specific peptide inhibitor gelatinases MMP-2 −9, cyclic CTTHWGFTLC (cyclic CTT), but not control peptide, STTHWGFTLS (STT), completely reversed vasodilation relaxin-treated rats. Comparable findings were observed with structurally different well-established, general antagonist MMPs, GM6001. In contrast, phosphoramidon, an endothelin-converting enzyme, did significantly change response administration. When incubated either MMP inhibitors, GM6001 or TIMP-2 ...