Hormonal influence on the release of endothelial nitric oxide: gender-related dimorphic sensitivity of rat aorta for noradrenaline.
Male gender shows a higher incidence of vascular disorders and this phenomenon could be explained by sexual dimorphic behaviour of vessels. Both gonadal hormones and endothelial nitric oxide (NO) are involved in the regulation of the vascular reactivity. This study aimed to evaluate a possible sexual dimorphic sensitivity of rat aorta for the catecholamine noradrenaline. To understand the role played by physiological concentrations of sex hormones, the experimental procedures were performed on isolated preparations from intact (sham-operated) and gonadectomized rats of both sexes. In parallel sets of experiments, the biosynthesis of NO was inhibited by N'-nitro-L-arginine methyl ester (L-NAME) to reveal any potential involvement of the endothelial modulator and its possible link with the endocrinous factor. In aortae from intact male and female rats, noradrenaline induced contractile effects with different potencies (mean+s.d. EC50 values 12.15 +/- 5.25 nM and 84.10 +/- 18.68 nM, respectively). Gonadectomy resulted in an increased sensitivity for noradrenaline in female vessels and a decreased sensitivity for the agonist in male vessels (EC50 values 25.64 +/- 5.04 nM and 21.70 +/ 1 1.13 nM, respectively). In aortae from intact male rats, the inhibition of NO biosynthesis resulted in a weak increase in sensitivity for noradrenaline (EC50 value 6.08 +/- 4.53 nM), whereas the increase was higher in vessels from intact female rats (EC50 value 10.38 +/- 8.40 nM). After treatment with L-NAME, aortae from gonadectomized male and female rats presented almost equivalent increases in sensitivity for the adrenergic agonist (EC50 values 6.02 +/- 3.63 nM and 9.10+/- 9.63 nM,respectively),and no significant difference in sensitivity could be recorded between intact and orchidectomized male rats, or between intact and ovariectomized female rats. It was concluded that rat aorta showed a sexual dimorphic sensitivity for noradrenaline and the female sex was more protected against the adrenergic contractile stimulus because of a higher release of endothelial NO. The gender-related difference in NO release was influenced by gonadal hormones, with the female hormones inducing an increase and the male hormones causing a reduction.
Calderone
Vincenzo
V
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università degli Studi di Pisa, Italy. calderone@farm.unipi.it
Baragatti
Barbara
B
Breschi
Maria Cristina
MC
Nieri
Paola
P
Martinotti
Enrica
E
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006728:Hormones / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology*; D009919:Orchiectomy; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006728:Hormones; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine