Affinity Constants and β-Adrenoceptor Reserves for Isoprenaline on Cardiac Tissue from Normotensive and Hypzrtensive Rats

Abstract

Abstract To determine whether there are differences in cardiac β-adrenoceptor responsiveness, isoprenaline affinity constants and fractional β-adrenoceptor occupancy—response relationships for isoprenaline in the early stages of established hypertension, we studied the effects of bromoacetylalprenololmenthane (BAAM) and ([3,5-diamino-6-chloro-N-(1[N-β-(2-hydroxyl-3-α-naphthoxypropylamino)ethylcarbamoyl]-1-methylethyl)-pyrazine-2-carboxamide (ICI 147 798), slowly reversible β-adrenoceptor antagonists, on the isoprenaline responses of the left ventricular papillary muscle and the left and right atria of 6-month-old Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The papillary muscles, but not the right and left atria, of the SHR were less responsive to isoprenaline than those of the WKY. The isoprenaline pD2 values (the negative logarithms of the molar concentrations of agonist producing 50% of the maximum response) were 7.72 and 8.00 on the SHR and WKY papillary muscles, respectively. On the WKY papillary muscle the isoprenaline KA values were 2–3 times 10−6M, which is as expected for isoprenaline at β1 or β2-adrenoceptors. Isoprenaline had 100-fold greater affinity on the WKY and SHR left atria than on the papillary muscles; the isoprenaline KA values were 2–4 times 10−8M. On the WKY papillary muscle and left atrium, isoprenaline had to occupy 3–4% of the β-adrenoceptors to produce a 50% maximum response; on the WKY papillary muscle and left atrium isoprenaline had to occupy 25–35% and 55%, respectively, of the β-adrenoceptors to produce a 90% maximum response. The SHR papillary muscles and left atrium had smaller β-adrenoceptor reserves for isoprenaline than did the WKY tissues. We were unable to obtain isoprenaline KA values on the WKY right atrium. The isoprenaline KA value on the SHR right atrium was 1–4 times 10−8M. Because the isoprenaline KA values for the left and right atria are markedly different from those previously reported for isoprenaline at β1 or β2-adrenoceptors, we suggest that atypical β-adrenoceptors might be present on the atria of WKY and SHR. We have also demonstrated a lower β-adrenoceptor reserve on SHR papillary muscle and atria in the early stages of established hypertension.