β-Andrenoceptors in the Hearts of Diabetic-hypertensive Rats: Radioligand Binding and Functional Experiments

Abstract

Beenen OHM, Batink HD, Pfaffendorf M, van Zwieten PA. β-Andrenoceptors in the hearts of diabetic-hypertensive rats: Radioligand binding and functional experiments.

Myocardial β-adrenoceptors and inotropic responses to β-adrenoceptor agonists were studied in isolated hearts obtained from diabetic and/or hypertensive rats. Streptozotocin diabetic Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), as well as normoglycaemic SHR-stroke prone rats were used. At the age of 18-20 weeks, β-adrenoceptor density was assessed in the left ventricle and isolated hearts were perfused according to Langendorff. Concentration response curves were made for dobutamine, salbutamol and the adenylyl cyclase activator forskolin. In both SHR and SHR-SP preparations a blunted inotropic response to β-adrenoceptor stimulation was observed, although responses to forskolin and β-adrenoceptor density and affinity were not different from those in normotensive hearts. In hearts taken from diabetic WKY and SHR, a decrease in β-adrenoceptor density was observed, but no parallel blunted response to β-adrenoceptor stimulation occurred. Moreover, the absolute (and percentual) inotropic responses to dobutamine and forskolin were increased in hearts from diabetic SHR when compared to their hypertensive norinoglycaemic controls. These results suggest an impaired activity of the stimulatory G-protein in hearts obtained from hypertensive rats, whereas the simultaneous occurrence of hypertension and diabetes may result in a compensatory increase in activity of the adenylyl cyclase activated pathway.

Key Words:

• adenylyl cyclase
• β-adrenoceptors
• β-adrenoceptor agonists
• diabetes mellitus
• forskolin
• G-proteins
• hypertension