Examination of cardiac alpha-adrenoceptors from pharmacological responses and radioligand binding. Comparison of rat and guinea pig tissues.
The object of this study was to determine suitable experimental conditions for the pharmacological evaluation of cardiac alpha-adrenoceptors. Atrial and ventricular preparations of the guinea pig and rat were employed, and the alpha-adrenoceptor responsiveness was compared with the binding of the alpha-adrenoceptor radioligand [3H]prazosin in membranes prepared from these cardiac regions. The experimental variables examined were the pacing frequency, bath temperature, choice of agonist, and cardiac region. In guinea pig atria the optimum alpha-adrenoceptor-mediated positive inotropic response to phenylephrine was at 32 degrees C and a pacing frequency of 1 Hz. A comparison of phenylephrine with methoxamine showed that the former yielded biphasic concentration-response curves in guinea pig left atria; the lower portion was alpha-adrenoceptor mediated and the upper, more substantial portion, was beta mediated. Methoxamine produced monophasic curves due entirely to alpha-adrenoceptor stimulation and was therefore used for comparisons between rat and guinea pig tissues. Of the guinea pig tissues, only the left atrium produced positive inotropic responses. Negative chronotropy was obtained with right atria and negative inotropy with ventricular strips and papillary muscles. The rat tissues all responded with positive responses, the largest maximum being in the left atrium. Binding data showed a larger number of alpha-adrenoceptors in the rat tissues, of which the ventricles had the greatest number. The lack of response of guinea pig ventricular tissues was therefore reflected in the low binding. From this study, the most appropriate model for characterizing cardiac alpha-adrenoceptors is therefore the rat left atria at 32 degrees C and paced at 1 Hz with methoxamine as the agonist.
D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008729:Methoxamine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity; D013696:Temperature
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D011433:Propranolol; D008729:Methoxamine