Effects of chronic administration of mestranol on alpha and beta adrenergic responsiveness in female rats

Several alpha and beta adrenergic responses were studied in female rats after treatment with a low dose of the synthetic estrogen, mestranol (15 micrograms i.p. biweekly), for 4 to 6 weeks and compared with untreated controls. The response of blood pressure to exogenously administered norepinephrine was measured in conscious rats by means of an indwelling catheter in the femoral artery. Basal systolic blood pressure was not different between control and treated groups, or was any difference observed in peak systolic pressure after acute i.v. administration of l-norepinephrine in concentrations of 0.0625, 0.125, 0.250 and 0.625 micrograms. In contrast, the half-time of the blood pressure response was significantly prolonged after administration of the various concentrations of norepinephrine to mestranol-treated rats. The half-time of the pressor response observed in control animals administered 0.625 micrograms of norepinephrine was elicited in mestranol-treated animals by only 0.250 micrograms of norepinephrine. Analysis of the time course of the pressor response indicates that mestranol treatment altered the duration of the blood pressure increase without an apparent change in the onset of the pressor response. No differences between groups were observed in beta adrenergic responsiveness measured in terms of the isoproterenol-induced increase in either heart rate (beta-1 response) or water intake (beta-2 response). Finally, the contractile response of aortic rings from mestranol-treated rats to both l-norepinephrine (10(-9) to 10(-5) M) and l-phenylephrine (10(-8) to 10(-4) M) was significantly less than that of aortic rings from control rats. These data indicate, therefore, that in vivo cardiovascular responsiveness to norepinephrine does not reflect the attenuated vascular reactivity of isolated aortic rings. Insofar as the dominant feature of the in vivo adrenergic response appears to be prolongation of pressor action, the present study suggests that processes involved in the inactivation of circulating norepinephrine may be altered by chronic treatment with a low-dose of mestranol.