VASCULAR BETA-ADRENOCEPTOR-MEDIATED RESPONSES IN HYPERTENSION AND AGING IN RATS

1 In normotensive Wistar (W) and spontaneously hypertensive (SHR) rats between 5 and 20 weeks of age, there was an age-related increase in blood pressure (r2=0.770 and r2=0.801 respectively). Except for adrenaline (r2=0.979) in SHRs, plasma catecholamines and age were unrelated. 2 In ring segments of thoracic aorta from 5, 10, 15 and 20 week old rats, the respective EC80s (-log m) for phenylephrine (PE)-induced contractions were 8.20+/-0.37, 7.96+/-0.10, 7.15+/-0.12 and 7.12+/-0.21 in W and 7.73+/-0.13, 7.72+/-0.16, 7.37+/-0.08 and 7.40+/-0.03 in SHR tissues (means+/-SEM; n=5-7). 3 In PE-preconstricted rings, the respective EC50s (-log m) for isoprenaline (IPNA)-induced relaxation were 7.97+/-0.11, 7.74+/-0.10, 6.96+/-0.19 and 6.57+/-0.26 in W and 8.03+/-0.24, 7.62+/-0.08, 6.88+/-0.13 and 6.73+/-0.14 in SHR tissues (n=5-7). 4 In PE-preconstricted rings from 5 and 20 week old rats, a single concentration of IPNA (approximating the respective IPNA EC50s) induced relaxation which was sustained over 2 h in W but not SHR tissues. The SHR:W ratios of the net relaxant responses, at 5 and 20 weeks, were 0.6461 and 0.6167 respectively. 5 Thus, W rats exhibit an age-related loss in both vascular alpha- and beta-adrenoceptor responsiveness which appears unrelated to plasma catecholamines. SHRs also exhibit an age-related loss in vasodilator beta-adrenoceptor responsiveness, which may involve adrenaline-induced desensitization, but appear to maintain vasoconstrictor alpha-adrenoceptor responsiveness. It is proposed that an age-related decline in beta-adrenoceptor responsiveness coupled to maintenance of alpha-adrenoceptor responsiveness may lead to chronic blood pressure elevation, as observed in SHRs, while a parallel decline in both alpha- and beta-adrenoceptor responsiveness, as observed in W rats, may preclude hypertension development.