It has been shown that nitric oxide (NO) is synthesized in the central nervous system as well as in vascular endothelial cells. However, the physiological role of NO in cardiovascular regulation by the central nervous system remains unclear. This objective of this study was to examine the possibility that NO plays a role in neural transmission in the nucleus tractus solitarius (NTS) and thus contributes to control of sympathetic nerve activity in rabbits. We examined the effects ofNG-monomethyl-L-arginine (L-NMMA), an inhibitor of the formation of NO from L-arginine, microinjected into the NTS on arterial pressure (AP), heart rate (HR), and renal sympathetic nerve activity (RSNA). L-NMMA increased AP and RSNA in rabbits with intact as well as denervated sinoaortic baroreceptors and vagi. L-NMMA increased HR only in rabbits with sinoaortic denervation and vagotomy. Pretreatment with L-arginine microinjected into the NTS, which did not alter baseline AP, HR, and RSNA, prevented the increases in AP and RSNA evoked with subsequent L-NMMA. Pretreatment with D-arginine did not alter the effects of subsequent L-NMMA injections into the NTS.
Animal studies suggest that some angiotensin coverting enzyme inhibitors augment endotheliumdependent vasorelaxation. We aimed to determine if captopril augments endothelium-dependent vasodilation in middle-aged hypertensive patients. By using strain-gauge plethysmography, forearm vasodilation evoked with intra-arteriaJ acetylchollne (4,8,16, and 24 /ig/min) or nitroprusside (0.2, 0.4, 0.8, and 1.2 /tg/min) was examined before and after captopril administration (25 mg per os). Before captopril, forearm vasodilation with acetylcholine was less in hypertensive patients (n=12) than in age-matched (n=7) or young (n=7) normotensive subjects, but forearm vasodilation with nitroprusside did not differ among the three groups. Captopril improved forearm vasodilation in hypertensive patients (n=l) with acetylcholine but nitroprusside did not In contrast, nifedipine (10 mg per os) did not alter forearm vasodilation with acetylcholine or nitroprusside in hypertensive patients (n=5). The decreases in mean blood pressure caused by captopril and nifedipine in hypertensive subjects were comparable. Captopril did not alter forearm vasodilation with acetylcholine or nitroprusside in young normotensive subjects (n=7). These results suggest that captopril in hypertensive patients may acutely improve impaired endothelium-dependent forearm vasodilation that does not result from reduction in blood pressure per se. I n experimental animals, chronic hypertension is associated with attenuated endothelium-dependent relaxation to acetylcholine (ACh). 1 -4 The impairment of endothelium-dependent relaxation in hypertension is closely correlated with the degree of hypertension and may improve after chronic antihypertensive therapy. -5 Recent studies in humans also have shown that endothelium-dependent forearm vasodilation to ACh is impaired in patients with essential hypertension. 6 -7 A recent study has suggested that lisinopril, an angiotensin converting enzyme inhibitor, increased compliance of the in situ isolated carotid arteries in the presence of the intact endothelium but did not alter it after endothelium removal in Wistar-Kyoto and spontaneously hypertensive rats.
This study was designed to Investigate the effects of L-arginine (the substrate of endothelium-derived nitric oxide) in human forearm vessels. We examined whether intra-arterial infusion of L-arginine dilated forearm vessels and augmented vasodilatory responses to acetylcholine in young, healthy humans. The left brachial artery was cannulated for drug infusions and direct measurement of arterial pressure. Forearm blood flow was measured by a strain gauge plethysmograph. Intra-arterial infusions of L-arginine at 10, 20, 40, and 60 mg/min increased forearm blood flow from 4.7±0.6 to 4.9±0.5, 5.7±0.5, 7.2±0.8, and 8.2±0.9 ml • min" 1 • 100 ml" 1 , respectively (n=8, p<0.01), whereas D-arginine at the same doses did not alter forearm blood flow (n=7). Intra-arterial infusions of acetylcholine (n=7) (4,8,16, and 24 /ig/min) and sodium nltroprusside (n=5) (0.2, 0.4, 0.8, and 12 /tg/mln) increased forearm blood flow dose dependently (p<0.01 for both). Arterial pressure was not altered with infusions of these drugs. Responses to acetylcholine were augmented with simultaneous intra-arterial infusion of L-arginine at 10 mg/ml (p<0.01) but not with D-arginine. Responses to sodium nitroprusside were not altered by L-arginine. These results in human forearm resistance vessels support the notion that vasodilation induced by acetylcholine is a result of the conversion from L-arginine to endothelium-derived nitric oxide. Our results suggest that intra-arterial infusion of L-arginine may facilitate production of nitric oxide in the forearm and that L-arginine contributes to the modulation of vascular smooth muscle tone in healthy humans. 1 - 4 The biosynthesis of nitric oxide by the endothelium accounts for the vasorelaxation, and nitric oxide is now considered one of the endothelium-derived relaxing factors (EDRF).5 -7 Nitric oxide is a potent and direct activator of soluble guanylate cyclase and increases the production of cyclic guanosine 3',5' monophosphate (cGMP). 5 -7 It is thought that acetylcholine dilates vessels by releasing nitric oxide from the endothelium. 8În in vitro experiments with normal vessels, it has been shown that L-arginine does not dilate vessels or augment acetylcholine-induced vasorelaxation. - 10- 15 It also has been shown that intravenous infusion of L-arginine does not augment acetylcholine-induced vasorelaxation in the hindquarter resistance vessels of normal rabbits. 16 In humans, it is not known whether L-arginine augments acetylcholine-induced vasodilation and whether L-arginine itself dilates blood vessels. In the present study, by measuring forearm blood flow with a plethysmograph, we examined whether intra-arterial infusion of L-arginine dilated forearm blood vessels and whether L-arginine augmented acetylcholine-induced vasodilation in the forearm of healthy humans. Methods General ProceduresSubjects were all young, healthy male students (age, 20-23 years) at our university who volunteered for the study. The protocol was explained, and written informed consent was obtained from each subject...
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