DISEASE-INDUCED CHANGES IN ALPHA-ADRENOCEPTOR-MEDIATED CARDIAC AND VASCULAR-RESPONSES IN RATS

1. The physiological relevance of cardiac and vascular alpha-adrenocep tors may increase in disease states in which beta-adrenoceptors are al tered. To test this, positive inotropic and vasoconstrictor responses to phenylephrine were measured in isolated tissues from rats with expe rimentally-induced hyperthyroidism, hypothyroidism and diabetes as wel l as in genetically spontaneous hypertensive rats (SHR). 2. In left at ria, positive inotropic responses to phenylephrine were increased in h ypothyroid and diabetic rats and abolished in hyperthyroid and SHR. 3. In contrast, phenylephrine produced increased positive inotropy in le ft ventricular papillary muscles from hyperthyroid rats, increased pot ency in diabetic rats and negative inotropic responses in hypothyroid rats. 4. The potency of phenylephrine as a vasoconstrictor in thoracic aortic rings was increased in hyperthyroid and SHR and decreased in h ypothyroid rats. 5. Thus, disease states which alter beta-adrenoceptor responsiveness can independently regulate atrial, ventricular and vas cular responses to the alpha(1)-adrenoceptor agonist, phenylephrine. T herefore, these disease states may alter the physiological control of the cardiovascular system by noradrenaline and adrenaline as well as t he responsiveness in disease states to therapeutic agents acting via a lpha-adrenoceptors.