THE FUNCTIONAL AND METABOLIC RESPONSES OF THE HEART TO CATECHOLAMINESARE ATTENUATED IN DIABETIC RATS

Many studies have shown that the contractile responses of the rat left ventricle is impaired in diabetes mellitus. Few studies have examined the acute in vivo effects of catecholamines on the right ventricle of diabetic rats. The present study investigates the acute in vivo effec ts of norepinephrine (100 mu g . kg(-1). h(-1) continuous intravenous infusion for 15 minutes) on the function of the right and left ventric le of diabetic rats. The effects of isoproterenol (25 mg . kg(-1), sub cutaneously) on the activity of glucose-6-phosphate dehydrogenase, the first and rate limiting enzyme of the oxidative pentose phosphate pat hway, and on adenine nucleotide biosynthesis of the diabetic heart wer e also examined. Diabetes mellitus was induced by a single intravenous injection of streptozotocin (60 mg . kg(-1)) 4 weeks before measureme nts. The hemodynamic meaurements were made on intact, anesthetized rat s with Millard ultraminiature pressure tip catheters. The basal hemody namic measurements (left ventricular systolic pressure, diastolic aort ic pressure, left ventricular dP/dt(max), right ventricular systolic p ressure and right ventricular dP/dt(max)) as well as glucose-6-phospha te dehydrogenase activity and adenine nucleotide biosynthesis were the same in the diabetic animals as in the controls. Heart rate was slowe r in the diabetics. Norepinephrine, after 15 minutes of intravenous in fusion, induced a marked increase in heart rate, left ventricular dP/d t(max), right ventricular systolic pressure and right ventricular dP/d t(max); whereas left ventricular systolic pressure and diastolic aorti c pressure remained unchanged. Isoproterenol caused a pronounced stimu lation of both cardiac glucose-6-phospate dehydrogenase activity (afte r 24 hours) and adenine nucleotide biosynthesis (after 5 hours). These stimulatory effects of norepinephrine and isoproterenol were signific antly reduced in the diabetic rat hearts.