INFLUENCE OF GENDER ON CONTROL OF ARTERIAL TONE IN EXPERIMENTAL-HYPERTENSION

Endothelial dysfunction has been found to be less severe in female tha n in male spontaneously hypertensive rats (SHR), which could contribut e to the gender differences observed in the extent and rate of progres sion of hypertension in SHR. However, the influence of gender on the r oles of different endothelium-derived mediators in the arterial respon ses in hypertension have not been evaluated in detail. Therefore, cont ractile and relaxation responses of mesenteric arterial rings in vitro were studied in female and male SHR, with normotensive female and mal e Wistar-Kyoto rats (WKY) serving as controls. In norepinephrine (NE)- precontracted arterial rings, endothelium-dependent relaxations to ACh as well as endothelium-independent dilations to sodium nitroprusside were more pronounced in female than in male SHR, whereas relaxations t o the P-adrenoceptor agonist isoproterenol remained equally impaired i n female and male SHR. The cyclooxygenase inhibitor diclofenac, which reduces the synthesis of dilating and constricting prostanoids, marked ly enhanced the relaxations to ACh in male SHR but not in the other gr oups. The nitric oxide (NO) synthase inhibitor N-G-nitro-L-arginine me thyl ester attenuated the relaxations to ACh more effectively in femal e SHR and WKY than in the male groups. However, when endothelium-depen dent hyperpolarization was prevented by precontracting the preparation s with KCl, no significant differences were found in relaxations to AC h among the study groups. In conclusion, release of cyclooxygenase-der ived constricting factors appeared to be more pronounced in male than in female SHR. In addition, the relative role of NO in endothelium-dep endent arterial relaxation seemed to be higher in female than in male SHR, and relaxation induced by an NO donor also was more pronounced in female than in male SHR.