Vasodilator-derived nitric oxide inhibits fetal calf serum- and angiotensin-II-induced growth of renal arteriolar smooth muscle cells.
Chemically derived nitric oxide (NO) and 8-bromo-cyclic-GMP (cGMP) have been shown to inhibit the growth of cultured aortic smooth muscle cells. However, their effects on growth of smooth muscle cells of resistance arteries have not been studied, although abnormalities in the control of such growth are related to the elevated vascular resistance in hypertension. This study evaluated the effects of three chemically dissimilar nitrovasodilators and cGMP on fetal calf serum (FCS)-induced growth of renal arteriolar smooth muscle cells (ASMCs). The compounds used were S-nitroso-N-acetylpencillamine (SNAP), sodium nitroprusside (SNP) and isosorbide-dinitrate (ISDN) and cell growth was evaluated in terms of DNA synthesis and cell number. In addition, the effects of vasodilator-derived NO on Angiotensin-II (Ang-II)-induced ASMC growth and contraction were studied. Treatment with 10(-7) to 10(-3) M SNAP, SNP or ISDN, as well as cGMP, inhibited FCS (5%)-induced DNA synthesis in a concentration-dependent manner (P < .01). These antimitogenic effects of SNAP, SNP and ISDN were inhibited by Hb (50 microM) and potentiated by superoxide dismutase (100 U/ml; P < .05). All compounds tested also inhibited FCS (5%)-induced proliferation of ASMCs (P < .01), with the order of potency being SNAP > SNP > ISDN > cGMP. SNAP (10(-6) M) inhibited cell proliferation induced by 10(-6) M Ang-II, but higher concentrations were required to inhibit ASMC proliferation induced by 5 and 10% FCS. Furthermore, NO generated from SNAP (10(-6) M) inhibited Ang-II (10(-6) M)-induced ASMC contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Dubey
R K
RK
Department of Medicine and Pharmacology, West Virginia University, School of Medicine, Morgantown.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D007668:Kidney / Q000098:blood supply*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
D014665:Vasodilator Agents; D000804:Angiotensin II; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D004247:DNA; D010396:Penicillamine; D006152:Cyclic GMP