Effects of inhibition of nitric oxide formation on basal vasomotion and endothelium-dependent responses of the coronary arteries in awake dogs.

Abstract

The role of nitric oxide in basal vasomotor tone and stimulated endothelium-dependent dilations in the coronary arteries in chronically instrumented awake dogs was studied by examining the consequences of inhibiting endogenous nitric oxide formation with the specific inhibitor of nitric oxide formation, NGmonomethyl-L-arginine (L-NMMA). In four awake dogs, coronary dimension crystals were chronically implanted on the circumflex artery for the measurement of epicardial coronary diameter, and Doppler flow probes were implanted for quantitation of phasic coronary blood flow (vasomotion of distal regulatory resistance vessels). Basal epicardial coronary diameter, acetylcholine-stimulated endothelium-dependent dilation, and flow-induced endothelium-dependent dilation of the epicardial arteries and phasic blood flow were recorded before, and after 5, 15, 50, and 120 mg/kg of L-NMMA. L-NMMA induced a dose-related increase in basal epicardial coronary vasomotor tone. There was an accompanying increase in aortic pressure and a decrease in heart rate. At doses 2 50 mg/kg, rest phasic coronary blood flow was also decreased. Left ventricular enddiastolic pressure and contractility were not significantly changed. In contrast, the flow-induced or acetylcholine-stimulated endothelium-dependent responses were attenuated only after infusion of the highest doses of L-NMMA (120 mg/kg). The changes in the basal vasomotor tone and acetylcholinestimulated endothelium-dependent responses returned towards the control states in the presence of L-arginine (660 mg/kg). These data support the view that nitric oxide plays a significant role in modulating basal vasomotion and endothelial-dependent dilation stimulated by acetylcholine or increase in blood flow in epicardial coronary arteries and also influence the regulation of coronary blood flow during physiologic conditions. (J. Clin.

Vascular and perivascular nitric oxide release and transport: Biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3)

“…This conclusion appears to contradict the experimental measurements showing that NO catalyzed by NOS3 expressed in the vascular endothelial cells regulates the basal vascular tone [32,[44][45][46]: hypertension or increased vascular tone has been measured in NOS3 knockout rats [46], and the shear stress-dependent NO production and the subsequent vasodilation of arterioles have also been documented in vivo [32]. The heterogeneous distribution of NOS isoforms may play a role in these phenomena [4,47].…”

Canine renovascular responses to sumatriptan and 5‐carboxamidotryptamine: modulation through endothelial 5‐HT1‐like receptors by endogenous nitric oxide

“…In addition, these inhibitors have Sumatriptan ({g kg-') 3 I _ Figure 4 Effects of i.v. administration of N0-nitro-L-arginine methyl ester (L-NAME, stippled columns, 10mg kg-'), and subsequently, L-arginine (hatched columns, 1000mg kg-'), upon (Whittle et al, 1989;Rees et al, 1990), rabbits (Rees et al, 1990), dogs (Chu et al, 1991) and in man (Vallance et al, 1990).…”

Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobin

“…11,19,20 In a normal vascular environment, NO synthesized by the endothelium and platelets promotes vasodilatation and inhibits platelet activation and aggregation as well as endothelial adhesion. [21][22][23][24][25][26] There is evidence in other diseases characterized by vascular dysfunction and impaired NO bioavailability that platelets are pathologically activated. 27,28 In addition, platelet activation has been observed in patients with pulmonary hypertension associated to ␤-thalassemia.…”