l- Arginine Restores the Effect of Ouabain on Baroreceptor Activity and Prevents Hypertension

Abstract

Abstract-In spontaneously hypertensive rats, ouabain exerts an excitatory effect on baroreceptor nerve activity (BNA).The aim of this study was to determine the effects of ouabain on BNA in other experimental models of hypertension and its interaction with nitric oxide. Rats were made hypertensive using the procedures for N -nitro-L-arginine methyl ester (L-NAME), deoxycorticosterone acetate (DOCA) salt, and 2-kidney, 1 clip (2K1C) hypertension models. In these groups, systolic arterial pressure was 195Ϯ7, 149Ϯ6, and 148Ϯ4 mm Hg, respectively, compared with 110Ϯ4 mm Hg in normotensive rats. Acute ouabain administration had an excitatory effect on BNA in normotensive rats (37Ϯ4%), an inhibitory effect in L-NAME hypertensive rats (Ϫ60Ϯ7%), and no effect in DOCA-salt and 2K1C hypertensive rats. The effects of ouabain were not related to arterial pressure levels, and no excitatory effect on BNA was observed in prehypertensive DOCA-salt rats. Long-term administration of L-arginine (3 g ⅐ kg Ϫ1 ⅐ day Ϫ1 ) prevented DOCA-salt (121Ϯ8 mm Hg) and 2K1C (104Ϯ4 mm Hg) hypertension, markedly attenuated L-NAME (130Ϯ9 mm Hg) hypertension, and restored the excitatory effect of ouabain on BNA in these groups to levels similar to the normotensive rats and their respective control groups. We conclude that ouabain has a diverse effect on BNA in experimental models of hypertension, and it can be normalized by L-arginine. The data also indicate that nitric oxide may play a pivotal role in mediating the excitatory effect of ouabain on BNA, and we speculate that a therapeutic combination of ouabain and L-arginine may be beneficial in secondary hypertension. Key Words: arginine Ⅲ ouabain Ⅲ L-NAME Ⅲ baroreceptors Ⅲ hypertension T he baroreflex acts to impede short-term fluctuations in arterial pressure (AP), 1 but it is impaired in pathological states such as long-term hypertension. 2 Although mechanical deformation of the nerve endings is considered the primary mechanism of baroreceptor activation, baroreceptor sensitivity is modulated by endothelial factors, such as nitric oxide (NO), which is known to inhibit baroreceptor nerve activity (BNA). 3 However, ionic mechanisms, including the inhibition of Na ϩ -K ϩ -ATPase pump activity, increase BNA. 4,5 Ouabain, which is known as an inhibitor of Na ϩ -K ϩ -ATPase pump activity, reportedly has an excitatory effect on BNA. 6,7 Recently, we reported that the excitatory effect of ouabain on BNA is increased in spontaneously hypertensive rats. 7 The purpose of the present study was to determine whether ouabain has an excitatory effect on BNA in deoxycorticosterone acetate (DOCA) salt and 2-kidney, 1 clip (2K1C) hypertensive rats. Because we did not observe such an effect in these models and because the high plasma volume could elicit greater vascular shear stress, which is a stimulus for NO, 8 we tried to restore the excitatory effect of ouabain on BNA in these models of hypertension by treating the animals with L-arginine long term. Additionally, we evaluated the effects of ouabain on BNA in N...

Cardiovascular Neural Reflexes in L-NAME–Induced Hypertension in Mice

“…The decrease in body weight in this group may be mainly caused by L-NAME treatment because NO seems to be involved in the regulation of appetite in mice. 14 During the baroreflex testing and consistent with observations in rats, [3][4][5] L-NAME-treated mice showed an attenuated pressor response to phenylephrine because, at least in part, the basal values of arterial pressure were already elevated. In contrast, it is conceivable that the exaggerated nitroprussideinduced hypotension in L-NAME mice could be caused by both the high basal arterial pressure levels and the direct donation of NO to the vessels.…”

“…At the end of treatment, the animals were anesthetized with urethane (1 mg/g IP), which is known to maintain a great portion of the cardiovascular reflexes, 5 and supplemental anesthesia was administered as needed. Because mice are susceptible to hypothermia, especially when anesthetized, they were placed on a warming pad (averaging 38°C) throughout the surgical procedure and experimental protocols.…”

“…It has also been shown that L-NAME hypertension in rats is characterized by changes in baroreflex control of cardiovascular function [3][4][5] and a profound enhancement of the Bezold-Jarisch cardiopulmonary reflex. 6 Although it has been demonstrated that chronic administration of L-NAME also leads to arterial hypertension in mice, 7 no previous studies have systematically evaluated the effects of chronic inhibition of NO synthase on the neural reflex control of cardiovascular function in mice.…”

Efeitos da crioterapia, estimulação elétrica transcutânea e da sua associação na atividade elétrica do nervo femoral em ratos

“…dose of Urethane (1mg.g -1 of body mass). This anesthetic was chosen because it is widely used in experiments which involve electrical activity, and therefore recommended for small changes in nerve activity 19,20 . The animals were placed in the supine position, and the femoral nerve of the right limb was exposed through a 1.5 to 2cm longitudinal rectilinear skin incision on the inner thigh (pelvic area).…”

Oral administration of L-arginine decreases blood pressure and increases renal excretion of sodium and water in renovascular hypertensive rats

“…These properties suggest that the level of NO production by the endothelium can play a pivotal role in the regulation of vascular tonus under both physiological and pathological conditions (12,13). Therefore, administration of exogenous L-Arg could, via production of NO, restore endothelial dysfunction and reduce blood pressure in experimental hypertension (14,15).…”