Diabetes potentiates acetylcholine-induced relaxation in rabbit renal arteries

Abstract

The response of rabbit renal arteries to acetylcholine and its endothelial modulation in diabetes were investigated. Acetylcholine induced concentration-related endothelium-dependent relaxation of renal arteries that was significantly more potent in diabetic rabbits G Ž . than in control rabbits. Pretreatment with N -nitro-L-arginine L-NOArg , indomethacin, or L-NOArg plus indomethacin induced partial inhibition of acetylcholine-induced relaxation. Inhibition induced by L-NOArg plus indomethacin was significantly higher in arteries from diabetic rabbits than in arteries from control rabbits. In renal arteries depolarised with KCl 30 mM and incubated with L-NOArg plus indomethacin, acetylcholine-induced relaxation was almost abolished in both groups of rabbits and this response was not different from that obtained in arteries without endothelium. Sodium nitroprusside induced concentration-dependent relaxation of renal arteries from control and diabetic rabbits without significant differences between the two groups of animals. These results suggest that diabetes potentiates the acetylcholine-induced relaxation in rabbit renal arteries. Increased release of nitric oxide and prostacyclin could be responsible for the enhanced relaxant potency of acetylcholine in diabetes. q

Experimental diabetes induces hyperreactivity of rabbit renal artery to 5-hydroxytryptamine

“…Moreover, the incubation of diabetic arterial segments with indomethacin enhanced the contractile response to 5-HT, thus suggesting that the endothelial arachidonic acid derivative of the cyclooxygenase via in diabetic arteries has vasodilator influence (probably prostacyclin). Our results are in agreement with the decreased activity of vasoconstrictor prostanoids (Makino and Kamata, 1998;Miranda et al, 2000a,b) and the enhanced activity of vasodilator prostanoids (Okumura et al, 2000;Alabadí et al, 2001) that have been reported in diabetes. It could be hypothesised that, in the experimental conditions of the present study, the absence of the vasoconstrictor prostanoid would be the expression of a compensatory mechanism addressed to minimise the deleterious consequences of both the hyperreactivity of renal artery to 5-HT and the defective participation of NO.…”

“…The maximal contraction induced by 5-HT in the presence of L-NA was significantly lower in renal arteries from diabetic rabbits than in those from control rabbits, thus suggesting that NO was less effective at inhibiting diabetic than control arteries, indicating a lower modulatory role of NO in the diabetic state. Previously, we have reported that the arterial response induced by the NO donor sodium nitroprusside is similar in renal arteries from control and diabetic rabbits, thus indicating that the sensitivity of smooth muscle cells of renal arteries to NO is not altered in our diabetic rabbits (Alabadí et al, 2001).…”

“…Diabetes enhances the inhibitory activity of the endothelium on 5-HT-induced contractions in rabbit carotid artery (Miranda et al, 2000b). Diabetes also enhances the endothelium-dependent relaxations to histamine (White and Carrier, 1986) and to acetylcholine (Bhardwaj and Moore, 1988;Pieper, 1999;Alabadí et al, 2001). In addition, the fact that in diabetic arteries without endothelium the 5-HT-induced contraction was higher than that obtained in control rabbits would suggest the existence of a diabetes-induced hyperreactivity of the renal arterial smooth muscle to 5-HT that would be partially deadened by the enhanced modulatory activity of the endothelium.…”

“…We have recently described that experimental diabetes induces changes in endothelial-mediated relaxant responses of rabbit renal (Alabadí et al, 2001) and carotid (Miranda et al, 2000a) arteries. In addition, we have also reported that diabetes enhances the sensitivity of the rabbit carotid artery to 5-HT (Miranda et al, 2000b).…”

Mechanisms underlying diabetes enhancement of endothelin-1-induced contraction in rabbit basilar artery

“…On the other hand, we have also reported alterations in the vascular response of diabetic animals to 5-hydroxytryptamine (Miranda et al, 2000a(Miranda et al, , 2002 and acetylcholine (Miranda et al, 2000b;Alabadí et al, 2001). The aim of the present study was to analyse the influence of alloxan-induced diabetes on the reactivity of the rabbit basilar artery to endothelin-1, including attention to endothelin-1 receptors and the endothelial modulatory mechanisms regulating this response.…”