title: The influence of sex hormones on vascular responses in the aorta of streptozotocin-diabetic male rats.
abstract: Diabetes mellitus reduces gender-related differences in the prevalence of cardiovascular disease by fading the vascular protective effects afforded by estrogen in females. However, the impact of estrogen treatment on and the contribution of androgens to vascular function in vessels from male diabetics are largely unknown. We investigated the effects of androgen deficiency and in vivo estrogen treatment by assessing the responsiveness to a number of vasoactive agents and the formation of eicosanoid mediators in aortic rings from intact and castrated streptozotocin-diabetic rats which had been implanted with 17beta-estradiol (E2) or its vehicle for 5 days. Castration was found to attenuate contractility to noradrenaline, to enhance tone-related release of NO, as shown by curves for N-methyl-L-arginine and superoxide dismutase (SOD), and to increase endothelium-dependent relaxation to carbachol and histamine, compared with intact animals. Smooth muscle sensitivity to exogenous NO and platelet thromboxane A2 production were unchanged but prostacyclin release by aortic tissue dropped by about 40% following castration. Treatment with E2 to intact animals still attenuated contractility to noradrenaline and potentiated relaxation to SOD and histamine but affected no other parameters. In contrast, when E2 was administered to castrated animals, responses to SOD, carbachol and histamine were significantly impaired. Thus, androgen deprivation appears to improve vascular function in male diabetic rats, whereas E2 treatment exerts some beneficial effects in intact, but not in castrated animals. Our findings therefore provide new insights into the role of sex hormones in the development of diabetic vascular complications.
authors.affiliation: Institute of Pharmacological Sciences, University of Milan, Italy. puglilab@mailserver.unimi.it
authors.forename: A
authors.initials: A
authors.lastname: Cignarella
authors.forename: C
authors.initials: C
authors.lastname: Bolego
authors.forename: C
authors.initials: C
authors.lastname: Pinna
authors.forename: R
authors.initials: R
authors.lastname: Zanardo
authors.forename: I
authors.initials: I
authors.lastname: Eberini
authors.forename: L
authors.initials: L
authors.lastname: Puglisi
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004347:Drug Interactions; D015777:Eicosanoids / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004967:Estrogens / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D015777:Eicosanoids; D004967:Estrogens; D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013311:Streptozocin; D009638:Norepinephrine