Acetylcholine and sodium nitroprusside cause long-term inhibition of EDCF-mediated contractions

Abstract

. Acetylcholine and sodium nitroprusside cause long-term inhibition of EDCF-mediated contractions. Am J Physiol Heart Circ Physiol 289: H2434 -H2440, 2005. First published July 22, 2005; doi:10.1152/ajpheart.00568.2005.-Preliminary studies suggested that previous exposure to acetylcholine (ACh) exerts a delayed inhibition of subsequent contractions mediated by endothelium-derived contracting factor (EDCF). To confirm this long-term inhibitory effect of ACh and to determine whether nitric oxide (NO) mediates the phenomenon, we suspended rings of spontaneously hypertensive rat (SHR) aortas in organ chambers for the recording of isometric force. The rings were incubated in the absence or presence of N -nitro-L-arginine methyl ester (L-NAME; inhibitor of NO synthases) or 1H-[1,2,4]oxadiazolo[4,3-␣]quinoxalin-1-one (ODQ; inhibitor of soluble guanylyl cyclase) before exposure to increasing concentrations of ACh or sodium nitroprusside (SNP) during contractions to phenylephrine. Thereafter, EDCF-mediated contractions to ACh or the calcium ionophore A-23187 were elicited. If the rings were preexposed to ACh or SNP, the subsequent ACh-induced EDCFmediated contractions were reduced compared with those obtained in rings of the same arteries not previously exposed to either agent. ODQ did not affect the inhibition caused by preexposure to ACh but significantly reduced that caused by preexposure to SNP. Previous exposure to SNP reduced, whereas previous exposure to ACh did not affect, endothelium-dependent contractions to A-23187. Previous exposure to either ACh or SNP did not affect the contractions to the thromboxane mimetic U-46619. Thus ACh and SNP exert delayed inhibition of EDCF-mediated contractions via distinct pathways. The effect of ACh is NO independent and upstream of the increase in calcium concentration that triggers the release of EDCF. The effect of SNP is downstream of the calcium rise and is mainly NO dependent. endothelium-dependent contractions; endothelium-derived contracting factors; spontaneously hypertensive rats; nitric oxide ACETYLCHOLINE (ACh) and other neurohormonal mediators evoke the simultaneous release of endothelium-derived relaxing factors (EDRF, in particular nitric oxide) and of endothelium-derived contracting factors (EDCF) to control the tone of the underlying vascular smooth muscle (10,16,23). However, as an artery ages or undergoes chronic hypertensive stress, the balance between EDRF and EDCF becomes dysfunctional to favor the production of EDCF (16, 17,32). In particular, EDCF-mediated contractions are prominent in the aorta of spontaneously hypertensive rats (SHR) (17, 38), but they also occur in arteries of other species (14,20,29,30). Endothelium-dependent contractions are mediated by products of cyclooxygenases (17, 32). The cyclooxygenases metabolize arachidonic acid into endoperoxides, which can be further broken down by enzymes forming prostaglandin E 2 , prostaglandin D 2 , prostaglandin F 2␣ , prostacyclin, and thromboxane A 2 (9). The precise prostaglandin accounting for ED...

Oxygen‐derived free radicals mediate endothelium‐dependent contractions in femoral arteries of rats with streptozotocin‐induced diabetes

“…This prompted the investigation of the role of oxygen-derived free radicals in the endothelium-derived contracting factor-mediated responses of the femoral artery of rats with STZ-induced diabetes. Because acetylcholine, the most commonly used agonist to evoke such responses in the rat aorta (Katusic et al, 1993;Yang et al, 2003b;Tang et al, 2005), does not cause such responses in the rat femoral artery (Shi et al, 2007), the calcium ionophore A23187 was selected for the present experiments.…”

“…To study endothelium-dependent contractions, all experiments were performed under quiescent conditions in the presence of L-NAME (N o -nitro-L-arginine methyl ester hydrochloride, 3 Â 10 À4 M; Auch-Schwelk et al, 1992;Yang et al, 2004a;Tang et al, 2005). The drugs were incubated in the organ chamber for 30 min before the administration of the calcium ionophore A23187 in a cumulative manner.…”

α1‐Adrenoceptor activation of PKC‐ε causes heterologous desensitization of thromboxane receptors in the aorta of spontaneously hypertensive rats

“…The sympathetic nervous system is hyperactive in the SHR (Head et al, 1985;Scott and Galway, 1985;Mangiarua and Lee, 1990;Ely et al, 1997). Thus, the interaction observed in the present study between the downstream effects of α1-adrenoceptor activation and the response to PGE2 may play a modulating role in reducing prostanoidinduced vasoconstriction in the SHR, in which such responses are prominent (Lüscher and Vanhoutte, 1986;Tang et al, 2005;Tang and Vanhoutte, 2008).…”

“…Aortae of 18-week-old SHR or WKY were incubated with the antagonist of TP receptors, S18886 (10 −6 M; Tang et al, 2005) for 40 min before obtaining contractions to increasing concentrations (10 −8 to 10 −5 M) of PGE2. S18886 abolished the response to the PG in either WKY or SHR preparations ( Figure 4A and B).…”

“…PGs and TXA2 can activate specific GPCRs -the prostanoid DP, EP, FP, IP and TP receptors respectively. However, in isolated arteries of the spontaneously hypertensive rat (SHR), PGs cause vasoconstriction mainly through activation of TP receptors (Tang et al, 2005;.…”