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Testosterone relaxes mesenteric microvessels by a non‐genomic mechanism that involves production of peroxynitrite from NOS
Author(s) -
Puttabyatappa Yashoda,
White Richard E
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.932.8
Subject(s) - peroxynitrite , vasodilation , chemistry , superoxide , endocrinology , mechanism of action , medicine , mesenteric arteries , nitric oxide , pharmacology , biochemistry , artery , in vitro , enzyme
The increased incidence of cardiovascular disease in men compared with premenopausal women suggests an unfavorable effect of male sex hormone testosterone (T2) on the cardiovascular system. Evidence indicates that T2 exerts acute vasorelaxing effects via non‐genomic mechanisms. These effects involve primarily the vascular smooth muscle (VSM). To date, the mechanism behind the vasodilatory action of testosterone is still under debate. Concentration‐response relationships for T2‐induced relaxation of rat mesenteric microvessels (1pM to 10 ìM) indicate a biphasic effect, and suggest a complex, non‐genomic mechanism of action. Rmax of T2‐induced relaxation is 36.45 ± 6, and was unchaged by actinomycin D, transcription inhibitor. Pretreatment with NOS blockers (L‐NAME, Rmax = 5.31 ± 1.58; L‐NPA, Rmax = 9.28 ± 1.54) did inhibit of T2‐induced microvascular relaxation. Moreover, it appears that T2 stimulates NOS activity via the PI3K‐ Akt pathway. We found that wortmanin, an Akt antagonist, inhibited the effect of T2 and immunoblot experiments confirmed this finding. Lastly, the effect of T2 was inhibited by peroxynitrite scavengers: uric acid (Rmax = 9.94 ± 3.52); FeTPPs (Rmax 15.81 ± 3.14) confirmed by fluorescence measurements. In conclusion, T2 induces relaxation of mesenteric microvessels is associated with production of both NO and superoxide which combine to form peroxynitrite. (supported by HL80402)