Evidence for the involvement of cyclic GMP in adenosine‐induced, age‐dependent vasodilatation

Abstract

1 Adenosine-induced dilatation of rat aorta was present in aorta taken from 4 week-old rats, attenuated with increase in age of rats to 8 weeks, and was virtually absent in the aorta from 12 week-old rats. 2 Removal of the endothelium by mechanical rubbing attenuated adenosine-induced dilatation. 3 Haemoglobin and methylene blue partly reversed the adenosine-induced endothelium-dependent dilatation. 4 The order of potency of adenosine derivatives was 5'-(N-ethylcarboxamido)indicating that adenosine receptors mediating the dilatation are of the A2 subtype. 5 [3H]-NECA bound to preparations of membranes from rats of 4 weeks old; it was displaced more effectively by NECA and the A2 ligand CV-1808 than by the A1 ligands CHA and S-PIA. ligands CHA and S-PIA. 6 The number but not affinity of specific binding sites for NECA decreased considerably with increase in age of rats to 8 weeks, and binding sites for [3H]-NECA were hardly detected in membrane preparations from rats of 20 weeks old. 7 Adenosine caused a marked increase in cyclic GMP production, but did not induce an increase in the cyclic AMP level. 8 This increase in cyclic GMP production induced by adenosine was abolished by methylene blue or 8-phenyltheophylline, or by removal of the endothelium. 9 The age-associated decrease in adenosine-induced dilatation was found to be associated with a reduction in the formation of cyclic GMP, but not of cyclic AMP. 10 These results suggest that adenosine causes dilatation via A2 receptors by inducing production of an endothelium-derived relaxing factor (EDRF), which in turn stimulates soluble guanylate cyclase, and so increases production of cyclic GMP. It is also suggested that the main reason for the age-associated decrease in adenosine-induced dilatation is a decrease in the number of A2-receptors or the ability of the endothelium to produce EDRF, leading to decreased production of cyclic GMP.

Involvement of nitric oxide pathway in the PAF‐induced relaxation of rat thoracic aorta

“…A decrease in the production/ accumulation of cyclic GMP which is known to be a second messenger in vascular relaxation (Rapoport & Murad, 1983), is undoubtedly the major cause of age-associated reduction of PAF-induced relaxation. Essentially similar age-dependent changes in relaxant responses and cyclic GMP production in rat thoracic aorta have been documented with histamine (Moritoki et al, 1986;, adenosine (Moritoki et al, 1990) and ATP (Ueda & Moritoki, 1991).…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…In guinea pig aorta, both A 1 and A 2 receptor subtypes were identified (Stoggall and Shaw, 1990), with some evidence for the expression of A 2B receptors (Martin, 1992). A 2 receptors are involved in endothelium-dependent relaxation of rat thoracic aorta (Moritoki et al, 1990;Rose'Meyer and Hope, 1990). Later articles have identified adenosine A 2A receptors as the mediators of rat aortic endothelium-dependent vasodilation (Lewis et al, 1994;Ray and Marshall, 2006;Nayeem et al, 2008), although A 2B receptors have also been implicated (Ansari et al, 2007a).…”

Contrasting effects of streptozotocin-induced diabetes on the in vitro relaxant properties of adenosine in rat pancreatic vascular bed and thoracic aorta

“…In order to avoid potential variation due to the difference in the individual vascular reactivity, the vascular preparations have been obtained from the same animal. Since STZ-induced diabetes is associated with a dramatic body weight loss and because adenosine-induced vasodilation is gradually diminished with advancing age in the rat (Moritoki et al 1990;Headrick 1996), two groups of control rats have also been considered: a group of weight and agematched rats, respectively. Additionally, despite the fact that the vascular effect of adenosine has classically been ascribed to an endothelium-independent process (Fredholm et al 1994), some workers have reported that its vascular relaxant effect was, at least in part, dependent on the presence of a functional vascular endothelium (Moritoki et al 1990;Rose'Meyer and Hope 1990;Abebe et al 1994;Lewis et al 1994).…”