Functional responses of the left and right heart of diabetic rats to alpha- and beta-adrenergic receptor stimulation.
It was the aim of the present study to examine the influence of alpha-and beta-receptor stimulation on the function of the right (RV) and left (LV) ventricle of streptozotocin-diabetic rats (STZ; 60 mg.kg-1; n = 14). Phenylephrine (PE; 3 mg.kg-1.h-1) or isoproterenol (ISO; 24 micrograms.kg-1.h-1) were infused intravenously for 20 min 4 weeks after STZ injection. The hemodynamic parameters were measured on intact, anaesthetized animals with special Millar ultraminiature tipcatheter manometers. In the non-diabetic animals (n = 15), PE caused a significant elevation of left ventricular systolic pressure (LVSP) from 138.5 +/- 3.2 to 205.4 +/- 7.5 mmHg and raised heart rate (HR) from 362 +/- 12.6 to 399 +/- 17.2 beats.min-1 (mean +/- S.E.M.; P < 0.05). LVSP and HR were significantly lower in the diabetic animals under control conditions (110.5 +/- 6.4 mmHg and 273 +/- 16.0 beats.min-1, respectively) and not affected by PE. ISO induced a significant and comparable decrease in diastolic aortic pressure (DAP) and an increase in HR in both the non-diabetic and diabetic group. The PE-induced enhancements of LV dP/dtmax and RV dP/dtmax from 10533 +/- 805 to 21533 +/- 1386 and from 2044 +/- 262 to 3867 +/- 733 mmHg.s-1 were significant in the control animals. In the diabetic rats, LV dP/dtmax was lower (5971 +/- 901 mmHg.s-1) and was increased by PE to the range of control rats (11171 +/- 1591 mmHg.s-1). The PE-induced elevation of RV dP/dtmax from 2028 +/- 284 to 2771 +/- 391 mmHg.s-1 was less pronounced in the diabetic rats than in the controls. Under the influence of ISO, the increase of dP/dtmax in both ventricles was comparable to the effect of PE and fully preserved in the diabetic animals. Right ventricular systolic pressure (RVSP) was increased under PE and ISO in both groups to comparable values. These results demonstrate that the in vivo response to beta-adrenoceptor stimulation is well preserved in the diabetic rat, while the effects of alpha-stimulation are markedly reduced, especially in the left ventricle and systemic circulation.
Irlbeck
M
M
Department of Physiology, University of Munich, FRG.
Zimmer
H G
HG
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D016277:Ventricular Function, Left / Q000187:drug effects*; D016278:Ventricular Function, Right / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D010656:Phenylephrine; D007545:Isoproterenol