Decreased Sensitivity of β-Adrenoceptors in Left Atria from Hypothyroid Rats
In isolated electrically driven (1.0 Hz, 37°C) left atria of normal rats (NR) as well as of those made hypothyroid (HR) by feeding with propylthiouracil the β-sympathomimetic effects of isoprenaline (IPN) and of phenylephrine (PE) in the presence of 10−5M yohimbine on force of contraction and on the cAMP-level were investigated. In HR the dose-response curves for the positive inotropic effects (PIE) of IPN and PE were shifted to the right in comparison to NR; thus, the pD2-value for IPN was significantly decreased from 8.39±0.07(N=8) to 7.99±0.1(N=4), that for PE from 5.44±0.08(N=5) to 4.93±0.08 (N=9). In NR a submaximal effective concentration (EC80 for the PIE) of IPN(3 × 10−8M) increased the cAMP-level after 60sec by about 60%; in HR, however, the same concentration produced only a 25% increase in cAMP. The EC80 for the PIE of PE(10−5M) increased in NR the cAMP-level by approximately 35%, but failed to increase it in HR. When used in three times higher concentrations, however, both agents produced in HR an increase of the cAMP-level comparable with the effects in NR.