1. The aim of the study was to characterize the functional beta 1-and beta 2-adrenoceptors of the rat left atrium and to investigate how these functional beta-adrenoceptor responses were altered in hypertension. The contractile responses of the left atrium from Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats to isoprenaline, T-0509 and procaterol were characterized. Subsequently, the effects of selective beta 1-(bisoprolol) and beta 2 (ICI 118,551)-adrenoceptor antagonists were investigated on these responses. 2. The maximal combined contractile responses of the rat left atrium to cardiac stimulation and CaCl2, isoprenaline, T-0509 or procaterol were not altered by hypertension. 3. The sensitivities to CaCl2 (pD2 on WKY left atrium = 2.99), isoprenaline (8.82) and T-0509 (8.84) were not altered by hypertension. There was an increase in sensitivity to procaterol from a pD2 value of 7.21 to 7.61 in the left atrium of the SH rat. 4. The basal tension induced by cardiac stimulation alone was inhibited by bisoprolol at > or = 10(-8) M and by ICI 118,551 at > or = 10(-7) M and this inhibitory effect is probably due to membrane stabilizing activity. 5. The pKB values for bisoprolol against isoprenaline, T-0509 and procaterol on the WKY were 8.43, 8.68 and 8.18, respectively, and were not different from SH rat left atrium. 6. The pKB value for ICI 118,551 against isoprenaline was increased from 7.06 on the WKY to 7.44 on the SH rat left atrium. The pKB values for ICI 118,551 against T-0509 and procaterol on the WKY were 7.18 and 8.14, respectively and were not significantly different from the SH rat left atrium values. 7. These results suggest that: (a) procaterol stimulates the beta 1-, in addition to, the beta 2-adrenoceptors of the rat left atrium; (b) functional beta 1-adrenoceptors are not altered in hypertension, and (c) there is probably an increase in the affinity of procaterol and isoprenaline for the beta 2-adrenoceptors which underlies the small increase in the functional beta 2-adrenoceptor response in hypertension.
The aim of the study was to determine whether the antagonism with pindolol, mepindolol and bopindolol at the beta 1-adrenoceptor of the rat left atria, a tissue with plenty of spare beta 1-adrenoceptors for isoprenaline maximum responses, was readily reversible or not. The effects of these drugs were compared to those of metoprolol, a readily reversible, and of ICI 147,798, an irreversible beta-adrenoceptor antagonist. Metoprolol at 10(-7) and 10(-6) M, ICI 147,798, pindolol, bopindolol (all at 10(-8) and 10(-7) M) and mepindolol at 10(-9) and 10(-8) M inhibited the cardiac stimulation responses to a small extent, which is indicative of membrane stabilizing activity, and also caused surmountable antagonism of isoprenaline responses. The inhibitory effects on the isoprenaline responses of metoprolol and pindolol were readily reversible, that of mepindolol was slowly reversible and those of ICI 147,798 and bopindolol were not reversed in 3 h. The inhibitory effects on isoprenaline responses of metoprolol at 10(-6) M, pindolol and bopindolol at 10(-7) M and mepindolol at 10(-8) M were at equilibrium, which is indicative of reversible, whereas the inhibitory effects of ICI 147,798 were increased, which is indicative of irreversible antagonism, when the beta-blocker treatment time was increased from 1 to 2 h. We conclude that the antagonism with pindolol at the beta 1-adrenoceptors of the rat left atria is readily reversible, that of mepindolol is slowly reversible and that of bopindolol is very slowly reversible.
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