Responsiveness, affinity constants and β-adrenoceptor reserves for isoprenaline on aortae from normo-, pre-and hypertensive rats

Abstract

Abstract The objective of this study was to determine the responsiveness, affinity constants and β-adrenoceptor reserves for isoprenaline on the isolated aorta in the maturation of normotensive and hypertensive rats. The effects of a very slowly reversible antagonist, bromoacetylalprenololmenthane (BAAM), on the relaxant responses of the aortae of 5- and 14-week-old Wistar kyoto normotensive rats (WkY) and spontaneously hypertensive rats (SHRs) to isoprenaline were determined. Five-week-old SHRs are pre-hypertensive and the aortic rings are less responsive to isoprenaline than age-matched WkY (pD2 values: WkY, 8.40; SHRs, 8.03). Similar relaxant responses to forskolin were obtained on the aortae of 5- and 14-week-old WkY and SHRs. The kA value for isoprenaline at the aortic β2-adrenoceptors of the 5-week-old WkY was 2.1 times 10−7 M, and similar values were obtained on the aortae of 5-week-old SHR and 14-week-old WkY and SHRs. In the maturation of the WkY aortae from 5 to 14 weeks, there was a reduction in the maximum response, a major loss of sensitivity and a loss of β2-adrenoceptor reserve for isoprenaline. On 5-week-old SHR aorta, the sensitivity to isoprenaline was 2.5-fold lower, and the β2-adrenoceptor reserve was less than on age-matched WkY. In the development of hypertension on the SHR aorta from 5 to 14 weeks, there was a reduction in the maximum response to isoprenaline. At 14 weeks, the sensitivity and the β2-adrenoceptor reserve to isoprenaline were similar, but the maximum responses were lower on the SHR than WkY. As there are differences in pre-hypertensive SHR and age-matched WkY aortic responses to isoprenaline, it is no longer valid to consider that the loss of responsiveness to isoprenaline in hypertension is solely owing to the hypertension. There are no changes in affinity, but major changes in the sensitivity, maximum responses and aortic β2-adrenoceptor reserves to isoprenaline in the maturation of normotensive and pre-hypertensive aortae.