Gender Differences in Hypertension in Spontaneously Hypertensive Rats: Role of Androgens and Androgen Receptor

Reckelhoff, Jane F.; Zhang, Huimin; Srivastava, Kumud; Granger, Joey P.

Hypertension 1999

                Studies have shown that males are at greater risk for cardiovascular disease as compared to age-matched females. In models of hypertension it has been shown that males have higher baseline blood pressure. The current study cites papers that state after the onset of puberty males have a higher blood pressure and this effect is attenuated by castration. Furthermore, this paper states that studies have shown that ovariectomies in female rats have no effect on the development of hypertension supporting the evidence that androgens mediate the higher blood pressure in males. The present study sought to determine if testosterone alone could cause hypertension in a spontaneously hypertensive rats.

                Male spontaneously hypertensive rats were obtained at 9 weeks for this study and maintained on standard diet with 12:12 light dark cycle. Rats were separated into three groups: first group was given a vehicle for control, the second group was given flutamide an androgen receptor antagonist, and the third group was given finasteride which is a drug that will prevent the conversion of testosterone to dihydrotestosterone. Rats were injected with these daily for 5-6 weeks. Rats were then anesthetized, and catheters were placed to measure blood pressure, sample blood, and measure renal blood flow and resistance.

                It was found that treatment with flutamide decreased mean arterial pressure in rats compared to control or finasteride treated rats. Renal plasma flow and glomerular filtration rate was not affected by the treatment of flutamide. Renal vascular resistance tended to be lower in rats treated with flutamide than in the controls. Compared to the control group, treatment with finasteride had no effect on arterial pressure of renal blood flow or glomerular filtration rate.

                Previous studies have suggested that the presence of androgens in males are responsible for males having higher blood pressure. Findings from the current study suggest that the mechanism behind this is via the androgen receptor. Other studies have shown that in male rats that lack the androgen receptor they have lower blood pressures that normal rats. Further data from the current study suggest that it is testosterone acting at the androgen receptor that is responsible for the development of hypertension and that this is independent of the ability to convert testosterone to dihydrotestosterone. The mechanism by which the androgen receptor mediates the hypertension in rats is unclear and needs to be further studied.

                I know that this is an old paper, however, I chose it because it poses an interesting question. Is it the androgens in males that cause the hypertension and not the estrogens in females that protect against it? This was also interesting to me because this study specifically states that other studies done by this group have shown that taking the ovaries out of females has no effect on the development of hypertension, which we know to not be true.

- Ben R