© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Increased myogenic tone in skeletal muscle arterioles of diabetic rats. Possible role of increased activity of smooth muscle Ca2+ channels and protein kinase C
From the Institutes of Pathophysiology, Pharmacology, and Department of Urology, Semmelweis University of Medicine, Budapest, Hungary and Department of Physiology, New York Medical College, Valhalla, New York, NY 10595, USA
* Correspondence author. Tel.: +1-914-594-4085; fax: +1-914-594-4018
Objective: The diabetes mellitus-induced microangiopathy is still not clearly characterized. In this study we aimed to elucidate the effect of streptozotocin (STZ)-induced diabetes on myogenic response of isolated rat skeletal muscle arterioles and the mechanisms responsible for its alterations. Methods: Male rats were divided into two groups: (1) control rats (C, plasma glucose: 6.4±0.5 mmol/l, n=40) 2) diabetic rats (DM, 65 mg/kg STZ iv, plasma glucose: 25.7±0.7 mmol/l, n=40). Changes in diameter of isolated, cannulated gracilis skeletal muscle arterioles (
130 µm in diameter) were measured by video-microscopy. Results: Step increases in perfusion pressure (PP; from 10 to 140 mmHg) elicited significantly greater constrictions in DM than in C gracilis arterioles, in the presence of the endothelium (E). Also, a step increase in PP (from 40 to 100 mmHg) elicited greater and faster constrictions in DM vs. C arterioles. There were no significant differences in the pressure-passive diameter (in Ca2+ free solution) curves of arterioles. Dilations to acetylcholine were impaired in arterioles of DM as compared to those of C rats (EC50, C: 4.0±0.9x10–9mol/l, DM: 4.8±2.0x10–8 mol/l (p<0.01), and unaffected by inhibition of nitric oxide synthesis with L-NNA (10–4 mol/l). Arteriolar constrictions to norepinephrine (NE) were significantly greater in DM compared to those of C rats (EC50, C: 6.2±0.6x10–7 mol/l, DM: 8.0±2.0 x10–8 mol/l, p<0.01) both in the presence and absence of E. In the absence of the E, constrictions to increases in pressure, or Ca2+ (0.25–7.5 mmol/l), or the voltage-dependent Ca2+-channel agonist Bay K 8644 (EC50; DM: 4.2±1.5x10–10 mol/l, C: 1.7±0.8x10–9 mol/l, p<0.05) or the protein kinase C activator phorbol 12-myristate 13-acetate (PMA, EC50; DM: 6±2x10–9 mol/l, C: 2±1x10–8 mol/l, p<0.05) were significantly greater in arterioles of DM compared to those of C rats. Conclusion: The novel findings of our study are that in diabetes mellitus the myogenic response of rat skeletal muscle arterioles is enhanced, which seems to be independent from the impaired endothelial function present simultaneously, and likely due to the increased activity of voltage-dependent Ca2+ channels and/or upregulation of protein kinase C in arteriolar smooth muscle.
KEYWORDS Microcirculation; Diabetes mellitus; Intraluminal pressure; Calcium sensitivity; Calcium channels; Protein kinase C; Rat
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