Functional studies on α₁‐adrenoceptor subtypes mediating inotropic effects in rat right ventricle

Abstract

1 We have studied the a1-adrenoceptor subtypes mediating inotropic effects of adrenaline in rat right ventricle and the Ca2+ sources used to elicit these effects. (ZlA-Adrenoceptor-mediated contractile effects in rat vas deferens were studied for comparison in some cases. 2 Treatment with chloroethylclonidine did not affect the maximal P-adrenoceptor-mediated inotropic effects in rat right ventricle or the maximal mlA-adrenoceptor-mediated contractile effects in rat vas deferens; it did not alter the potency of isoprenaline in the ventricle and reduced the potency of the o-adrenoceptor antagonists in vas deferens only slightly. Treatment of right ventricular strips with CdCl2 markedly reduced resting tension and enhanced maximal inotropic effects of isoprenaline but did not affect its potency. In control ventricles the organic Ca2`entry blocker, nitrendipine and treatment with the inorganic Ca2+ entry blocker, CdCl2 did not reduce inotropic effects of adrenaline whereas ryanodine treatment inhibited them. In contrast, nitrendipine and CdCl2 treatment had major inhibitory effects in chloroethylclonidine-treated but lacked inhibitory effects in phenoxybenzamine-treated ventricular strips. 6 We conclude that inotropic effects of adrenaline in rat heart are mediated mainly by aBadrenoceptors via release of Ca2+ from an intracellular pool. Following inactivation of z1B-adrenoceptors by chloroethylclonidine treatment, alA-adrenoceptors can fully compensate and mediate inotropic effects by promoting influx of extracellular Ca2+ at least partly via voltage-operated channels. Therefore, we speculate that aB-adrenoceptors exert a tonic inhibitory effect on (XA-adrenoceptors.

Pharmacological Characterization and Cross Talk of α1A- and α1B-Adrenoceptors Coexpressed in Human Embryonic Kidney 293 Cells

“…Cross talk of ␣ 1A -and ␣ 1B -ARs has been reported previously in rat myocardium (Michel et al, 1994b;Deng et al,1998). Results with double ␣ 1a -and ␣ 1b -AR knockout mice have indicated that both ␣ 1a -and ␣ 1b -ARs may be required for cardiac hypertrophy (O'Connell et al, 2003).…”

alpha 1‐adrenoceptor‐mediated negative inotropy of adrenaline in rat myocardium.

“…However, conflicting results have been reported with regard to the allocation of distinct physiological effects to the respective receptor subtypes. In rat ventricular myocardium (Michel, Hanft & Gross, 1994) and in rabbit ventricular myocardium (Takanashi, Norota & Endoh, 1991) the positive inotropic effect of adrenaline was found to be mediated mainly by alB-adrenoceptors. In another study on rat myocardium the positive inotropic effect of phenylephrine was antagonized by blocking the alA-adrenoceptors with WB 4101 (2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane), but not affected by the alB antagonist, chlorethylclonidine (Nagashima, 1994).…”

Characterization of α1D‐adrenoceptor subtype in rat myocardium, aorta and other tissues

“…BMY 7378 inhibited [3H]-prazosin binding to right ventricular membranes (Table 1), antagonized the inotropic effects of phenylephrine (Table 2) and inhibited the phenylephrineinduced increase in PI turnover (Figure 4) (Michel et al, 1989;Yazawa & Honda, 1993) as well as to liver membranes, which contain xlB-adrenoceptors (Han et al, 1987;Faure et al, 1994). It should nevertheless be emphasized that although OlD-adrenoceptor mRNA is expressed in rat myocardium (Perez et al, 1994;Price et al, 1994;Rokosh et al, 1994;Stewart et al, 1994), it represents less than 5% of the total al-adrenoceptor mRNA (Scofield et al, 1995) and the inotropic effects of the al agonists are mainly produced TI via a1A-and alB-adrenoceptors (Michel et al, 1994b;Deng et 7 8 al., 1996). Taking into account these data, findings of the present study suggest a minor role for myocardial LXIDadrenoceptors in the inotropic responses to al agonists.…”