Influence of chronic treatment of rats with isoprenaline and calcium channel blockers on response of isolated right ventricle to noradrenaline.

Influence of chronic treatment of rats with and calcium channel blockers (CCBs) and isoprenaline (ISP) on responses to noradrenaline (NA) was investigated on electrically--driven isolated right ventricle preparations. The ventricles were obtained from animals treated with chronic ISP or CCBs alone and chronic nifedipine, verapamil, diltiazem or nimodipine plus chronic ISP. A decreased response to NA as evidenced by an increase in EC50 for contraction which was observed in chronic ISP- treated preparations may be due to development of desensitisation (down-regulation) of beta-adrenoceptors. In chronic CCB-treated preparations there was a significant decrease in the EC50 of NA and decreased contractile response suggesting an increase in the beta-adrenoceptors and decreased availability of calcium, respectively. In chronic CCBs + ISP treated preparations further decreases in the EC50 values were observed suggesting that the voltage gated L-type Ca2+ channels may be affected directly or indirectly by change in beta-adrenoceptor activity. By the above results a proposed mechanism of interrelationship of beta-adrenoceptors with voltage gated L-type calcium channels in cardiac muscle is supported.

Interaction of calcium channel blockers with different agonists in aorta from normal and diseased rats.

The interactions of calcium channel blockers (CCBs) with noradrenaline (NA), phenylephrine (PE), dopamine (DA) and KCl have been investigated in rat isolated aortic strip. In preparations from control and hypertensive (DOCA-saline) rats chronically treated with verapamil, nifedipine and diltiazem, there was partial inhibition of contractions to NA, PE and DA. However, with nimodipine, there was potentiation of responses. This could be related to the occurrence of different isoforms of L-type calcium channels. In preparations obtained from hyperthyroid rats the concentration-response curves of NA, PE and KCl were shifted to the right with depressed maximal response which could be secondary to the primary effect exerted on the heart. In preparations from L-thyroxine + nimodipine/nifedipine treated rats the concentration-response curves of NA, PE and KCl were shifted to the right and the maxima was depressed suggesting that this may be due to decreased alpha receptor density (NA and PE) and down-regulation of voltage operated channels (KCl).

Interaction of calcium channel blockers (CCBs) with histamine and 5-hydroxytryptamine in aorta from normal and diseased rats.

The present study attempts to investigate the interaction of calcium channel blockers (CCBs) with histamine (H) and 5-hydroxytryptamine (5-HT) in rat isolated aortic strip preparations. In preparations obtained from rats chronically treated with various CCBs the contractile responses to H were completely blocked suggesting that this may be due to inhibition of the voltage-dependent channels and inositol 1,4,5-triphosphate induced release of calcium from intracellular stores. The decreased contractions of the aortic strip preparations with 5-HT obtained from rats chronically treated with various CCBs implies a decrease in 5-HT receptor density. DOCA-saline hypertensive rats chronically treated with various CCBs showed variable responses to H and 5-HT suggesting that these changes may be due to different isoforms of L-type calcium channels. In L-thyroxine-treated preparations or those simultaneously treated with L-thyroxine and CCBs the responses to H were abolished and those to 5-HT were partially blocked with decrease in maxima which could be secondary to the primary effect on the heart and to generalised reduced senstivity of the rat aorta.