Ouabain Produces Diverse Excitatory Effects on Afferent Baroreceptor Nerve Activity in SHR and WKY Animals

Abreu, Gláucia Rodrigues de; Neto, H.A. Futuro; Cabral, Antônio M.; Vasquez, Elisardo C.

doi:10.3109/10641969809053208

Cited by 12 publications

(15 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In rats with chronic SAD, the same treatment for only 5 days increased BP to the same extent as in intact rats treated with ouabain for 12 days. Consistent with a previous study, 13 the present study shows that, in Wistar rats, ouabain administered peripherally sensitizes arterial baroreflex function. Thus, in rats treated long term with ouabain, it appears that, sensitization of the arterial baroreflex temporarily inhibits central sympathoexcitatory and pressor effects of ouabain and that the central effects of ouabain at the present dose prevail after a few days of delay.…”

Section: Baroreflex Sensitization and Exogenous Ouabain-induced Hypersupporting

confidence: 81%

See 1 more Smart Citation

Digoxin Prevents Ouabain and High Salt Intake–Induced Hypertension in Rats With Sinoaortic Denervation

et al. 1999

View full text Add to dashboard Cite

Abstract-Digoxin prevents ouabain-induced hypertension in rats. In the present study, we tested whether this effect of digoxin depends on its sensitizing effect on baroreflex function or is due to an antagonistic action on exogenous ouabain or endogenous ouabainlike activity ("ouabain") in the brain. In Wistar rats, resting mean arterial pressure (MAP) was significantly increased by long-term subcutaneous (SC) ouabain (75 g/d) plus high salt (8%) intake for 12 days (but not after only 5 days). In rats with chronic sinoaortic denervation (SAD), MAP was increased within 5 days of ouabain treatment to the same extent as MAP after 12 days of treatment in intact rats. The effect of ouabain and high salt was prevented when digoxin was given SC concomitantly via osmotic minipump (200 g ⅐ kg Ϫ1 ⅐ d Ϫ1 ). Resting MAP was not changed in rats treated with digoxin alone. In a second set of rats with chronic SAD or sham surgery, high salt intake was given for 14 days, with or without SC digoxin (200 g ⅐ kg Ϫ1 ⅐ d Ϫ1 ) or intracerebroventricular (ICV) antibody Fab fragments (200 g/d), which bind "ouabain" with high affinity. On day 14, MAP, central venous pressure, heart rate, and renal sympathetic nerve activity were recorded in conscious rats at rest and in response to air-jet stress, IV phenylephrine and nitroprusside, and acute volume expansion with 5% dextrose IV. In rats with SAD versus sham surgery, high salt significantly increased resting MAP as well as excitatory responses of MAP, heart rate, and renal sympathetic nerve activity to air stress. These effects of high salt in rats with SAD were prevented by digoxin or Fab fragments. Arterial baroreflex function was blunted but cardiopulmonary baroreflex function was not affected in rats with SAD. Digoxin and Fab fragments had no effects on either function. In an in vitro assay for the inhibitory effects on Na ϩ ,K ϩ -ATPase activity, 20 ng of ouabain caused 29% inhibition, but 20 ng of ouabain plus 13 or 53 ng of digoxin caused only 16% or 4% inhibition, respectively. These data indicate that the arterial baroreflex opposes sympathoexcitatory responses to ouabain and "ouabain" in the brain, thereby delaying ouabain-and preventing high salt-induced hypertension in Wistar rats. In addition to possible effects on the arterial baroreflex, digoxin appears to act centrally to prevent the sympathoexcitatory and pressor effects of increased brain "ouabain" or ouabain. Key Words: digoxin Ⅲ nerve activity, sympathetic, renal Ⅲ sodium intake Ⅲ baroreflex Ⅲ ouabain Ⅲ denervation, sinoaortic Ⅲ stress, air Ⅲ Fab H igh salt intake increases endogenous compounds with ouabainlike activity ("ouabain") in the brain of rats with salt-sensitive blood pressure (BP) and to a lesser extent in the brain of normotensive rats with salt-insensitive BP. 1,2 In saltsensitive rats, such as spontaneously hypertensive and Dahl salt-sensitive rats, the increase in brain "ouabain" appears to mediate salt-induced sympathetic hyperactivity, impairment of baroreflex function, and hypertension. [3][4][5][6]...

show abstract

Section: Baroreflex Sensitization and Exogenous Ouabain-induced Hypersupporting

confidence: 81%

“…10,12 Peripherally administered ouabain can sensitize arterial baroreceptors. 13 This sensitization may be responsible for temporarily offsetting central pressor effects of ouabain, thereby leading to the delay of ouabain-induced hypertension.Digoxin is structurally similar to ouabain but has been reported to prevent ouabain-induced hypertension in normo- …”

mentioning

confidence: 99%

Digoxin Prevents Ouabain and High Salt Intake–Induced Hypertension in Rats With Sinoaortic Denervation

et al. 1999

View full text Add to dashboard Cite

show abstract

“…In contrast to our previous observations in spontaneously hypertensive rats, 7 in the present study, we observed that ouabain injection did not increase BNA in DOCA-salt and 2K1C hypertensive rats. A reasonable explanation for the enhanced response of spontaneously hypertensive rats to ouabain could be an active mechanism of production of ouabain-like substances in this strain.…”

Section: Discussioncontrasting

confidence: 56%

“…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.…”

mentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 1999

Self Cite

View full text Add to dashboard Cite

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...

show abstract

Acute Pressor Actions of Ouabain Do Not Enhance the Actions of Phenylephrine or Norepinephrine in Anesthetized Rats

Barker

Rossoni²,

Vassallo³

2001

Journal of Cardiovascular Pharmacology

View full text Add to dashboard Cite

The inhibition of high-affinity isoforms of the Na+,K+-ATPase by nanomolar levels of ouabain has been proposed to enhance the actions of vasoconstrictor agents that act via a Ca+2-dependent mechanism. The present study tested this hypothesis by evaluating the effects of ouabain (6 and 18 microg/kg, i.v.) on the vasopressor actions of phenylephrine and norepinephrine in anesthetized, reflex-blocked rats. In separate groups of animals, dose-response curves for increases in diastolic pressure produced by phenylephrine were generated after the administration of saline (control), ouabain (18 microg/kg), L-omega-N-nitro arginine methyl ester (L-NAME, 3 micromol/kg) and angiotensin II (15 ng/kg per min). Treatment with ouabain (18 microg/kg) produced an increase in diastolic pressure of 19+/-3 mm Hg but did not significantly alter the potency or maximal response produced by phenylephrine. In contrast, treatment with angiotensin II and L-NAME, agents known to enhance the actions of alpha-adrenoceptor agonists, increased the potency of phenylephrine. In animals in which the pressor actions of norepinephrine were evaluated before and after the administration of ouabain (6 microg/kg), ouabain did not alter the pressor response to norepinephrine. Blockade of alpha-adrenoceptors with phentolamine was found to attenuate as well as partially reverse the increase in diastolic pressure produced by ouabain. These observations suggest that ouabain produces a pressor response by actions on sympathetic nerve endings as well as on vascular smooth muscle and that these actions do not alter the sensitivity to phenylephrine or norepinephrine.

show abstract

Ouabain Produces Diverse Excitatory Effects on Afferent Baroreceptor Nerve Activity in SHR and WKY Animals

Cited by 12 publications

References 13 publications

Digoxin Prevents Ouabain and High Salt Intake–Induced Hypertension in Rats With Sinoaortic Denervation

Digoxin Prevents Ouabain and High Salt Intake–Induced Hypertension in Rats With Sinoaortic Denervation

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

Acute Pressor Actions of Ouabain Do Not Enhance the Actions of Phenylephrine or Norepinephrine in Anesthetized Rats

Contact Info

Product

Resources

About