The functional and metabolic responses of the heart to catecholamines are attenuated in diabetic rats.
Many studies have shown that the contractile response 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 effects of norepinephrine (100 micrograms.kg-1.h-1 continuous intravenous infusion for 15 minutes) on the function of the right and left ventricle of diabetic rats. The effects of isoproterenol (25 mg.kg-1, subcutaneously) on the activity of glucose-6-phosphate dehydrogenase, the first and rate limiting enzyme of the oxidative pentose phosphate pathway, and on adenine nucleotide biosynthesis of the diabetic heart were also examined. Diabetes mellitus was induced by a single intravenous injection of streptozotocin (60 mg.kg-1) 4 weeks before measurements. The hemodynamic measurements were made on intact, anesthetized rats with Millard ultraminiature pressure tip catheters. The basal hemodynamic measurements (left ventricular systolic pressure, diastolic aortic pressure, left ventricular dP/dtmax, right ventricular systolic pressure and right ventricular dP/dtmax) as well as glucose-6-phosphate dehydrogenase activity and adenine nucleotide biosynthesis were the same in the diabetic animals as in the controls. Heart rate was slower in the diabetics. Norepinephrine, after 15 minutes of intravenous infusion, induced a marked increase in heart rate, left ventricular dP/dtmax, right ventricular systolic pressure and right ventricular dP/dtmax; whereas left ventricular systolic pressure and diastolic aortic pressure remained unchanged. Isoproterenol caused a pronounced stimulation of both cardiac glucose-6-phosphate dehydrogenase activity (after 24 hours) and adenine nucleotide biosynthesis (after 5 hours).(ABSTRACT TRUNCATED AT 250 WORDS)
Irlbeck
M
M
Department of Physiology, University of Munich, Germany.
Zimmer
H G
HG
D000227:Adenine Nucleotides / Q000096:biosynthesis*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects / Q000378:metabolism*; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013566:Sympathomimetics / Q000494:pharmacology*
D000227:Adenine Nucleotides; D013566:Sympathomimetics; D005954:Glucosephosphate Dehydrogenase; D007545:Isoproterenol; D009638:Norepinephrine