Effect of Alpha- and Beta-Adrenergic Blocking Agents on the Increase in Renin Secretion Produced by Stimulation of the Renal Nerves

Loeffler, Judith; Stockigt, Jan R.; Ganong, William F.

doi:10.1159/000122112

Cited by 79 publications

(36 citation statements)

References 7 publications

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“…This reduction supports the hypothesis that a significant portion of vasodilatory drug-induced renin release is mediated by the beta-adrenergic component of the sympathetic nervous system. This interpretation is consistent with that of Loeffler and his associates (16) who have shown that direct stimulation of renal nerves in anesthetized dogs causes renin release and that this response can be blocked with propranolol. An increase in circulating catecholamines can also contribute to renin release by a betaadrenergic mechanism (6), and this effect would likewise be blocked by propranolol.…”

Section: Discussionsupporting

confidence: 92%

Adrenergic Component of Renin Release Induced by Vasodilating Antihypertensive Drugs in the Rat

Pettinger

Campbell

Keeton

1973

Circulation Research

100

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The capacity of the vasodilating drugs, minoxidil and hydralazine, for inducing renin release was characterized in rats according to chronology and dose response. Propranolol inhibition of this renin release was also characterized and related to serum levels of propranolol. Minoxidil and hydralazine (1.0 mg/kg) induced sevenfold elevations of serum renin activity. Treatment with propranolol, resulting in plasma propranolol concentrations as low as 50 ng/ml, impaired vasodilatory drug-induced renin release. The propranolol inhibition suggests a beta-adrenergic component to this type of renin release and the potential for a clinically efficacious drug interaction. KEY WORDS hydralazineangiotensin beta-receptor blockade propranolol minoxidil• The combination of a vasodilating drug and propranolol can control hypertension in man without precipitating many untoward effects (1-5).Vasodilating agents elicit renin release from the kidney which results in elevated serum renin activity and increased angiotensin formation (6, 7). The angiotensin thus formed probably antagonizes the antihypertensive effect of vasodilating drugs (8) such as hydralazine and minoxidil. Since combined therapy with propranolol and vasodilating drugs has been found to be particularly effective (1-5), this study was designed to characterize vasodilatory drug-induced renin release in the rat and to determine the effect of beta-receptor blockade on this release.Methods Male Wistar rats (180-250 g) were housed in individual cages and exposed to light by an automated system from 6 AM to 6 PM. The rats ingested tap water and Purina rat chow containing 152 mEq sodium/kg ad libitum.Both hydralazine and minoxidil were administered intraperitoneally, and propranolol was injected subcutaneously. An equal volume (0.5 ml) of saline was administered as a placebo to the control rats. Doses of drugs were calculated for the salt in mg/kg.Propranolol was solubilized in 0.9% NaCl by adding several drops of glacial acetic acid. Propranolol was administered subcutaneously because of the constant, sustained plasma levels following this route of administration (Fig. 1). Intraperitoneal injection of propranolol resulted in a rapid rise and fall and a high degree of variability in serum levels among the rats. Alternatively, subcutaneous administration resulted in more sustained plasma propranolol levels with minimal variability among the rats. Thus, the sustained plateau (Fig. 1) from the subcutaneous administration permitted the experiments to be done at relatively constant, predictable propranolol serum levels.In the experiments involving beta-receptor blockade, propranolol was injected at 0 time and the vasodilating drug was injected at 10 minutes; the rats were decapitated at 30 minutes. The rats treated with a vasodilating drug alone or with saline were killed 20 minutes after injection.At the times indicated in Results, the unanesthetized rats were decapitated, and aortic blood samples were collected in iced, siliconized glass tubes during the first 4 secon...

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Section: Discussionsupporting

confidence: 92%

Adrenergic Component of Renin Release Induced by Vasodilating Antihypertensive Drugs in the Rat

Pettinger

Campbell

Keeton

1973

Circulation Research

100

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“…8 The kidney contains both ␣-and ␤-adrenoreceptors that respond to sympathetic stimulation with increased renin secretion. 9 Hypertension in several animal models, including the spontaneously hypertensive rat (SHR), is believed to be related to increased adrenergic activity. 10,11 Increased activity of both splanchnic and renal nerves has been reported in SHR versus normotensive Wistar-Kyoto control rats.…”

mentioning

confidence: 99%

Renin Activity and Blood Pressure in Response to Chronic Episodic Hypoxia

1999

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Abstract-Previous studies in several strains of rats have demonstrated that 35 days of recurrent episodic hypoxia (EH) (7 hours per day), with a fractional concentration of inspired oxygen that produces desaturation equivalent to the recurrent hypoxemia of sleep apnea, results in an 8 to 13 mm Hg persistent increase in diurnal systemic blood pressure (BP). Carotid chemoreceptors and the sympathetic nervous system have been shown to be necessary for development of this BP increase. Both renal artery denervation and adrenal demedullation block the BP response to chronic EH. The present study was undertaken to define further the role of the kidneys and the renin-angiotensin system in this BP increase. Separate groups of male Sprague-Dawley rats had either (1) bilateral renal artery denervation with EH, (2) sham surgery with EH, (3) sham surgery with sham EH (compressed air), (4) EH with losartan, (5) unhandled with losartan, or (6) unhandled. The experimental period lasted 35 days. Both renal-artery denervated and losartan-treated animals showed no BP change or a lowering of BP in response to EH, whereas the sham-operated EH animals showed a progressive, sustained increase in resting room air BP. BP remained at basal levels or fell in unhandled and unhandled losartan-treated animals. Plasma renin activity was elevated 4-fold versus basal levels in EH animals with renal nerves intact but remained at baseline levels in denervated animals. At the end of the experiment, renal tissue catecholamines confirmed renal denervation in those animals. In conclusion, EH causes a progressive increase in BP, mediated in part through renal sympathetic nerve activity that acts to increase renin-angiotensin system activity through angiotensin II type 1 receptors. (Hypertension. 1999;34:309-314.)Key Words: hypoxia Ⅲ blood pressure Ⅲ denervation, renal Ⅲ sympathetic nervous system Ⅲ sleep apnea syndromes Ⅲ hypertension, systemic Ⅲ renin-angiotensin system R ecent publications have implicated increased sympathetic nervous system activity, driven by chemoreceptor response to progressive hypoxemia, as a contributing cause of acute elevation of blood pressure (BP) in patients with obstructive sleep apnea. 1-3 The mechanism for sustained diurnal rise in BP after many years of repetitive apnea remains a mystery, but chronic stimuli, including recurrent episodic hypoxia (EH), repeated arousals, or repetitive Mueller maneuvers, may contribute to it.We have developed a rat preparation that mimics the hypoxic changes seen in sleep apnea patients. With the use of individual cylindrical cages and a method for rapid exchange of inspired concentration of oxygen (FiO 2 ) to as low as 2% to 3%, arterial oxyhemoglobin saturation falls acutely to levels of Ϸ70% to 75%. Such EH, when administered repetitively (every 30 seconds for 7 hours per day for 35 days), increases resting, diurnal mean arterial pressure (MAP) by 8 to 13 mm Hg. 4 Chemoreceptor denervated 5 and chemical sympathectomy rats (neurotoxin 6-OH dopamine) 6 show no increase in MAP following...

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“…* 0 - 81 In fact, studies of renal cortical slices indicate that a-adrenergic receptor stimulation of the juxtaglomerular cell with methoxamine does not increase renin release. * 4 The present investigation suggests that the marked increase in renin release with methoxamine is mediated via stimulation of the vascular ai-adrenergic receptor. The present results further suggest that this vascular a^receptor mechanism is stimulated only with marked reduction in renal blood flow.…”

Section: *"mentioning

confidence: 50%

Acute and chronic intrarenal alpha- and beta- adrenergic receptor stimulation of renin release in the conscious dog.

Ayers¹,

Katholi²,

Carey³

et al. 1981

Hypertension

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Effect of Alpha- and Beta-Adrenergic Blocking Agents on the Increase in Renin Secretion Produced by Stimulation of the Renal Nerves

Cited by 79 publications

References 7 publications

Adrenergic Component of Renin Release Induced by Vasodilating Antihypertensive Drugs in the Rat

Adrenergic Component of Renin Release Induced by Vasodilating Antihypertensive Drugs in the Rat

Renin Activity and Blood Pressure in Response to Chronic Episodic Hypoxia

Acute and chronic intrarenal alpha- and beta- adrenergic receptor stimulation of renin release in the conscious dog.

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