AFFINITY CONSTANTS AND BETA-ADRENOCEPTOR RESERVES FOR ISOPRENALINE ONCARDIAC TISSUE FROM NORMOTENSIVE AND HYPERTENSIVE RATS

To determine whether there are differences in cardiac beta-adrenocepto r responsiveness, isoprenaline affinity constants and fractional beta- adrenoceptor occupancy-response relationships for isoprenaline in the early stages of established hypertension, we studied the effects of br omoacetylalprenololmenthane (BAAM) and ylcarbamoyl]-1-methylethyl)-pyr azine-2-carboxamide (ICI 147 798), slowly reversible beta-adrenoceptor antagonists, on the isoprenaline responses of the left ventricular pa pillary muscle and the left and right atria of 6-month-old Wistar Kyot o rats (WKY) and spontaneously hypertensive rats (SHR). The papillary muscles, but not the right and left atria, of the SHR were less respon sive to isoprenaline than those of the WKY. The isoprenaline pD(2) val ues (the negative logarithms of the molar concentrations of agonist pr oducing 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 K-A values were 2-3 x 10(-6) M, which is as expected for isoprenaline at beta(1) or beta(2)-adrenoceptors. Isoprenaline had 100 -fold greater affinity on the WKY and SHR left atria than on the papil lary muscles; the isoprenaline K-A values were 2-4 x 10(-8) M. On the WKY papillary muscle and left atrium, isoprenaline had to occupy 3-4% of the beta-adrenoceptors to produce a 50% maximum response; on the WK Y papillary muscle and left atrium isoprenaline had to occupy 25-35% a nd 55%, respectively, of the beta-adrenoceptors to produce a 90% maxim um response.The SHR papillary muscles and left atrium had smaller beta -adrenoceptor reserves for isoprenaline than did the WKY tissues. We w ere unable to obtain isoprenaline K-A values on the WKY right atrium. The isoprenaline K-A Value on the SHR right atrium was 1-4 x 10(-8) M. Because the isoprenaline K-A values for the left and right atria are markedly different from those previously reported for isoprenaline at beta(1) or beta(2)-adrenoceptors, we suggest that atypical beta-adreno ceptors might be present on the atria of WKY and SHR. We have also dem onstrated a lower beta-adrenoceptor reserve on SHR papillary muscle an d atria in the early stages of established hypertension.