Role of the Sympathetic Nervous System in the Onset of Hypertension in the Rat: The Effect of 6‐oh‐dopamine

Li, Ming; Whitworth, Judith A.

doi:10.1111/j.1440-1681.1991.tb01432.x

Cited by 14 publications

(9 citation statements)

References 17 publications

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“…A similar effect of NAC on α-adrenergic pathways in mesenteric beds of SHR has been reported (35). However, enhanced sympathetic activity is not essential for the development of glucocorticoid-induced hypertension in humans (37) and chemical sympathectomy with 6-OH-dopamine failed to prevent ACTH-hypertension in SD rats (38). Thus, it is unlikely that the same mechanism is in play.…”

Section: Discussionsupporting

confidence: 54%

N-Acetylcysteine Antagonizes the Development But Does Not Reverse ACTH-Induced Hypertension in the Rat

Mondo

Zhang

Possamai

et al. 2006

Clinical and Experimental Hypertension

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We investigated the effect of antioxidant N-acetylcysteine (NAC) on adrenocorticotropic hormone (ACTH)-hypertension. Male Sprague-Dawley rats received NAC (10 mg/L) or water 4 days before ACTH/saline treatment for 13 days (prevention study). In a reversal study, NAC commenced on day 8 of ACTH/saline treatment and continued for 5 days. ACTH increased systolic blood pressure (SBP) in water drinking rats (111 +/- 1 to 131 +/- 3 mmHg, p < 0.001). In the prevention study, NAC + ACTH increased SBP (108 +/- 2 to 120 +/- 2 mmHg, p < 0.001) but less than ACTH alone (p' < 0.05). In the reversal study, NAC had no significant effect (132 +/- 4 to 124 +/- 3 mmHg, ns). Thus, NAC partially prevented but did not reverse ACTH-induced hypertension.

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Section: Discussionsupporting

confidence: 54%

N-Acetylcysteine Antagonizes the Development But Does Not Reverse ACTH-Induced Hypertension in the Rat

Mondo

Zhang

Possamai

et al. 2006

Clinical and Experimental Hypertension

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“…42 Our data suggest that both systems sustain elevated blood pressure during ACTH excess. In the rat, neither chemical sympathectomy 43 nor chronic V1 receptor antagonism 44 fully prevent the pressor response to ACTH. ACTH-induced hypertension is also observed in Brattleboro rats, indicating that vasopressin is not essential.…”

Section: Discussionmentioning

confidence: 96%

Mineralocorticoid and Glucocorticoid Receptors Stimulate Epithelial Sodium Channel Activity in a Mouse Model of Cushing Syndrome

2009

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Abstract-Experiments in Cushing patients and healthy control subjects receiving adrenocorticotropic hormone (ACTH) indicate that transient renal sodium retention may contribute to the generation of hypertension. Here we have investigated the effect of chronic ACTH infusion on renal sodium handling in adult male C57BL/6J mice using selective antagonists to dissect mineralocorticoid and glucocorticoid receptor-mediated pathways. Mice were infused via osmotic minipump with ACTH (2.5 g/d) or saline for 2 weeks before being anesthetized for renal function experiments. ACTH caused an increase in blood pressure and a reduction in fractional sodium excretion associated with enhanced activity of the epithelial sodium channel. Given separately, spironolactone and RU38486 blunted the pressor response to ACTH and the increased epithelial sodium channel activity; combined mineralocorticoid and glucocorticoid receptor blockade was required to resolve the response to ACTH excess. Dietary sodium depletion also prevented ACTH-induced hypertension. The effect of increased sodium reabsorption in the distal nephron is offset by downregulation of Na-K-Cl cotransport in the loop of Henle. Sodium excretion is normalized chronically, but blood pressure remains high; acute blockade of V1 receptors and ␣1 adrenoceptors in combination restored blood pressure to control values. In summary, ACTH excess promotes renal sodium reabsorption, contributing to the increased blood pressure; both glucocorticoid and mineralocorticoid receptor pathways are involved. These data are relevant to conditions associated with overactivity of the hypothalamic-pituitary-adrenal axis, such as obesity and chronic stress.

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“…Acute hypoxia has been shown to increase myocardial norepinephrine turnover in rats 41 - 42 and guinea pigs, 43 but chronically increased sympathetic activity is usually associated with no change or a decrease in tissue catecholamine levels. 33 Since chronically administered intermittent hypoxia (4 continuous hours per day, 24-75 exposures) is a known potent stimulus to pulmonary artery vasoconstriction and right ventricular stress and hypertrophy, 44 -47 one could speculate that sympathetic activity to the right heart might be differentially increased over that of the left in the present model. The fact that right ventricular hypertrophy was not seen in the current study is consistent with results in our previous studies.…”

Section: Figure 3 Bar Graph Shows Right Ventricular (Rv) and Left Vementioning

confidence: 89%

“…Pretreatment with 6-OH dopamine has been used to prevent development of hypertension in certain rat models, including SHR 32 and adrenocorticotropic hormone-induced hypertension. 33 However, some results concerning the antihypertensive effect of 6-OH dopamine in SHR are contradictory, indicating that the effect may be transient or depend on which portion of the denervated adrenergic vasculature controls hypertension. 34 The success of this experiment depended on the injection of enough 6-OH dopamine to maintain chemical sympathectomy while avoiding the direct acute blood pressure-lowering effects of the drug.…”

Section: Figure 3 Bar Graph Shows Right Ventricular (Rv) and Left Vementioning

confidence: 99%

Sympathetic denervation blocks blood pressure elevation in episodic hypoxia.

et al. 1992

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We have previously described a rat model that responds to repetitive episodic hypoxia (FiO 2 nadir 3-5% for 12 seconds every 30 seconds for 7 hr/day for 35 days) with chronic increase in arterial blood pressure. The purpose of the current study was to determine if peripheral sympathetic nervous system denervation blocks this persistent blood pressure elevation. Chemical sympathetic denervation was achieved and maintained by three intraperitoneal injections (100 mg/kg 6-hydroxydopamine) on days 1, 3, and 27 of a 47-day experiment in two groups of rats. One denervated group was subjected to episodic hypoxia for 40 consecutive days beginning on day 7 and the other remained unhandled in their usual cages. A third group was injected with vehicle only and subjected to the same episodic hypoxia while a fourth group remained unhandled for 40 days. The vehicle-treated, episodic hypoxia-exposed group showed a 7.7 mm Hg increase in mean arterial blood pressure (conscious, unrestrained) over the 40-day period, whereas all other groups showed a decrease in mean arterial pressure. The left ventricle and septum/whole body weight ratio was higher in both episodic hypoxia-exposed groups at the end of the study. Plasma epinephrine in both groups administered 6-hydroxydopamine was higher on day 6 than in the vehicle-injected rats. Measurement of catecholamines in cardiac muscle homogenate confirmed denervation in 6-hydroxydopamine animals. These results indicate that the peripheral sympathetic nervous system is necessary for the persistent increase in blood pressure in response to repetitive episodic hypoxia. emia is associated with acute elevation of blood pressure, and in up to 50% of patients with chronic apnea, persistent elevation of daytime blood pressure is seen. '-3 Repetitive acute hypoxia with heightened sympathetic nerve activity could play an important role in the persistent elevation of blood pressure seen in some patients.With some species variability, acute hypoxemia causes increased heart rate, variable changes in arterial pressure, and increased cardiac contractility and output through stimulation of central and peripheral chemoreceptors and perhaps other local effects.4 -6 The effector arm of this reflex involves increased sympathetic discharge. Plasma norepinephrine is elevated in acute hypoxia, 7 -8 and urinary catecholamine elevation in patients with severe sleep apnea is reversed by tracheostomy.9 Acute hypoxia induces elevated blood pressure and increased microneurographic amplitude, implying increased postganglionic sympathetic activity. 1011 In spontaneously hypertensive rats (SHR) 12 and in humans with borderline hypertension, the sympathetic response to acute hypoxia is exaggerated. 13 The response is further exaggerated in borderline hypertensive humans when apnea is added to acute hypoxia.14 Finally, muscle nerve sympathetic activity recorded during apnea in humans shows a progressive increase throughout the apnea followed by an abrupt reduction at apnea termination. 15A key concept in the above hy...

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Role of the Sympathetic Nervous System in the Onset of Hypertension in the Rat: The Effect of 6‐oh‐dopamine

Cited by 14 publications

References 17 publications

N-Acetylcysteine Antagonizes the Development But Does Not Reverse ACTH-Induced Hypertension in the Rat

N-Acetylcysteine Antagonizes the Development But Does Not Reverse ACTH-Induced Hypertension in the Rat

Mineralocorticoid and Glucocorticoid Receptors Stimulate Epithelial Sodium Channel Activity in a Mouse Model of Cushing Syndrome

Sympathetic denervation blocks blood pressure elevation in episodic hypoxia.

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