Difference in Pressor Responses to NG-Monomethyl-L-Arginine between Conscious and Anesthetized Rats.

Aisaka, Kazuo; Mitani, Aki; Kitajima, Yasuo; Ohno, Tomochika; Ishihara, Takafumi

doi:10.1254/jjp.56.245

Cited by 25 publications

(6 citation statements)

References 12 publications

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“…The blood pressure-raising effect of L-NMMA recently has been found to be much greater in anesthetized than in conscious rats. 30 L-NMMA doses comparable to those used in our human subjects produced increases in blood pressure in conscious rats that were comparable (approximately 10 mm Hg) to those seen in conscious humans but approximately four times larger in either chloralose-urethaneor pentobarbital-anesthetized rats. Given that a substantial fraction of this large increase in blood pressure is thought to be sympathetically mediated, the possibility exists that studies in anesthetized animals may have significantly overestimated the importance of neuronal NO in the regulation of blood pressure.…”

Section: Lbnpsupporting

confidence: 60%

Is nitric oxide involved in the tonic inhibition of central sympathetic outflow in humans?

1994

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Recent studies in experimental animals have advanced the concept that neuronal nitric oxide is an important component of the signal transduction pathways that tonically restrain sympathetic vasoconstrictor outflow from the brain stem. To determine whether or not this concept can be extended to the control of sympathetic outflow in humans, we recorded muscle sympathetic nerve activity (microelectrodes, peroneal nerve) in healthy human subjects during intravenous infusion of the nitric oxide synthase inhibitor N G -monomethyl-L-arginine (L-NMMA) (3.6 to 6.7 tng/kg). The major new finding is that during intravenous L-NMMA mean arterial pressure increased (10±2 mm Hg, P<.05), whereas heart rate and sympathetic nerve activity decreased (P<.05) by 10±2 beats per minute and 61 ±5%, respectively. These reflex decreases were indistinguishable from those produced when S tudies in experimental animals have provided unequivocal evidence that endogenous synthesis of nitric oxide (NO) from L-arginine is of major importance in the tonic regulation of vasomotor tone and blood pressure.13 However, much less is known about the importance of NO in the regulation of the human cardiovascular system.In numerous species, pharmacological inhibitors of NO synthase such as /V°-monomethyl-L-arginine (L-NMMA) cause a robust increase in blood pressure that at first was attributed solely to inhibition of endothelial NO synthase. 49 However, the presence of NO synthase in specific brain regions such as the nucleus tractus solitarius and rostral ventrolateral medulla suggested that NO also might be involved in the central neural control of blood pressure.1012 Based on these neuroanatomic findings, several recent studies have implicated a major neurogenic component in the blood pressure increase produced by inhibition of NO synthesis: it is accompanied by increases in heart rate and sympathetic nerve activity (SNA) and is greatly attenuated by ganglionic blockade. 1317In intact rats, for example, intravenous L-NMMA produces a sustained elevation in blood pressure with a biphasic response in renal SNA: there is an initial transient decrease in SNA caused by baroreflex activation followed by a sustained increase in SNA caused by central neural activation.13 Thus, the increase in SNA was (1) augmented after denervation of sinoaortic baroreceptors and cardiopulmonary vagal afferents, (2) eliminated by cervical spinal cord transection, and (3) duplicated by microinjection of L-NMMA into the nucleus tractus solitarius in rabbits or the rostral ventrolateral medulla in cats and rats.13 " 16 Taken together, these extensive studies in experimental animals advanced the concept that the neuronal isoform of NO synthase is an important component of the signal transduction pathways that tonically restrain sympathetic vasoconstrictor outflow from the brain stem.A key unanswered question is whether or not this concept can be extended to the control of sympathetic outflow in conscious humans. To address this question, we recorded postganglionic SNA ta...

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Section: Lbnpsupporting

confidence: 60%

Is nitric oxide involved in the tonic inhibition of central sympathetic outflow in humans?

1994

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“…Most of the studies were performed on anesthetized rats and an important question is whether these data can be extrapolated to the conscious state during the evolution of hypertension. In conscious rats, acute intravenous infusion of L-NMMA causes a much smaller increase in blood pressure than in anesthetized rats (13). In addition, acute hypertension induced by L-NMMA in conscious humans was accompanied by a decrease in sympathetic nerve activity (14).…”

Section: Introductionmentioning

confidence: 97%

Sympathetic activation in rats with L-NAME-induced hypertension

Biancardi

Bergamaschi

Lopes

et al. 2007

Braz J Med Biol Res

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We evaluated the hemodynamic pattern and the contribution of the sympathetic nervous system in conscious and anesthetized (1.4 g/kg urethane, iv) Wistar rats with L-NAME-induced hypertension (20 mg/ kg daily). The basal hemodynamic profile was similar for hypertensive animals, conscious (N = 12) or anesthetized (N = 12) treated with L-NAME for 2 or 7 days: increase of total peripheral resistance associated with a decrease of cardiac output (CO) compared to normotensive animals, conscious (N = 14) or anesthetized (N = 14). Sympathetic blockade with hexamethonium essentially caused a decrease in total peripheral resistance in hypertensive animals (conscious, 2 days: from (means ± SEM) 2.47 ± 0.08 to 2.14 ± 0.07; conscious, 7 days: from 2.85 ± 0.13 to 2.07 ± 0.33; anesthetized, 2 days: from 3.00 ± 0.09 to 1.83 ± 0.25 and anesthetized, 7 days: from 3.56 ± 0.11 to 1.53 ± 0.10 mmHg mL -1 min -1 ) with no change in CO in either group. However, in the normotensive group a fall in CO (conscious: from 125 ± 4.5 to 96 ± 4; anesthetized: from 118 ± 1.5 to 104 ± 5.5 mL/min) was observed. The responses after hexamethonium were more prominent in the hypertensive anesthetized group. However, no difference was observed between conscious and anesthetized normotensive rats in response to sympathetic blockade. The present study shows that the vasoconstriction in response to L-NAME was mediated by the sympathetic drive. The sympathetic tone plays an important role in the initiation and maintenance of hypertension.

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“…However, the mechanisms underlying the NO deficiency‐induced hypertension are not fully understood. Initially, the increase in blood pressure was exclusively attributed to a consequence of withdrawal of the vasodilator actions of NO, and therefore, studies were focused on its vascular actions with little consideration for a role of NO in other tissues (Rees et al, ; Vallance et al, ; Aisaka et al, ; Guix et al, ). Currently, considering the pleiotropic actions of NO (e.g., its involvement in the control of brain functions), another mechanism, such as the sympathetic vasomotor activation, has been noted as an important mechanism underlying the hypertension induced by NO synthesis blockade (Bergamaschi et al, ; Peotta et al, ; Esler et al, ).…”

Section: Introductionmentioning

confidence: 99%

Pattern of sympathetic vasomotor activity in a model of hypertension induced by nitric oxide synthase blockade

et al. 2019

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We aimed to investigate the effects of nitric oxide (NO) synthesis inhibition by NO synthase inhibitor N‐nitro‐L‐arginine‐methyl ester (L‐NAME) treatment on the sympathetic vasomotor nerve activity (SNA) on two sympathetic vasomotor nerves, the renal and splanchnic. NO plasma level and systemic oxidative stress were assessed. Hypertension was induced by L‐NAME (20 mg/kg per day, by gavage, for seven consecutive days) in male Wistar rats. At the end of the treatment, blood pressure, heart rate, arterial baroreflex sensitivity, renal SNA (rSNA), and splanchnic SNA (sSNA) were assessed in urethane anesthetized rats. L‐NAME‐treated rats presented increased blood pressure (152 ± 2 mmHg, n = 17) compared to the control group (101 ± 2 mmHg, n = 15). Both rSNA (147 ± 10, n = 15 vs. 114 ± 5 Spikes/s, n = 9) and sSNA (137 ± 13, n = 14 vs. 74 ± 13 spikes/s, n = 9) were significantly increased in the L‐NAME‐treated compared to the control group. A differential response on baroreflex sensitivity was found, with a significant reduction for rSNA but not for sSNA arterial baroreceptor sensitivity in L‐NAME‐treated rats. The adjusted regression model revealed that the reduction of systemic NO levels partially explains the variation in sSNA and blood pressure, but not rSNA. Taken together, our data show that hypertension induced by NO synthase blockade is characterized by increased SNA to the rSNA and sSNA. In addition, we found that the rats that had the greatest reduction in NO levels in plasma by L‐NAME were those that developed higher blood pressure levels. The reduction in the NO level partially explains the variations in sSNA but not in rSNA.

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Difference in Pressor Responses to NG-Monomethyl-L-Arginine between Conscious and Anesthetized Rats.

Cited by 25 publications

References 12 publications

Is nitric oxide involved in the tonic inhibition of central sympathetic outflow in humans?

Is nitric oxide involved in the tonic inhibition of central sympathetic outflow in humans?

Sympathetic activation in rats with L-NAME-induced hypertension

Pattern of sympathetic vasomotor activity in a model of hypertension induced by nitric oxide synthase blockade

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