α_1b‐Adrenoceptors mediate renal tubular sodium and water reabsorption in the rat

Abstract

1 It is known that activation of a,-adrenoceptors causes renal vasoconstriction and increased tubular Na+ and water reabsorption, with the (xi.-subtype mediating the constrictor effect.2 This study examines which subtype of ox,-adrenoceptors mediates tubular Na+ and water reabsorption in pentobarbitone-anaesthetized rats. In order to avoid systemic effects, phenylephrine (0.3 to 30 yg kg-'), methoxamine (0.1 g kg-1) and vehicle were infused into the right renal artery (via the suprarenal artery) of three groups of rats. Two other groups of rats were continuously infused with the irreversible selective Mlb-adrenoceptor antagonist, chloroethylclonidine (3 mg kg-' h-') for 1 h, prior to the construction of dose-response curves to phenylephrine or methoxamine. Another group was continuously infused with the irreversible selective 'zla-adrenoceptor antagonist, SZL49 (10 fig kg-I h-') for 1 h, prior to the construction of dose-response curves to phenylephrine. Mean arterial pressure (MAP), heart rate (HR), urine flow, Na+ and K+ excretion, and urine osmolality were monitored. 3 Phenylephrine and methoxamine did not affect MAP or HR but dose-dependently and significantly decreased urine flow, urine osmolality as well as Na+ excretion and, slightly increased K+ excretion, although this was significant only for phenylephrine. 4 The antidiuretic, antinatriuretic and kaliuretic effects of phenylephrine were abolished by pretreatment with chloroethylclonidine, but were not inhibited by SZL49. The inhibitory effects of methoxamine on urine flow and Na+ excretion were also almost totally abolished by chloroethylclonidine. 5 Our results show that Oclb-adrenoceptors mediate renal tubular Na+ and water reabsorption.

2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults

“…Sympathetic activation can increase ventricular volumes and pressure by causing peripheral vasoconstriction 336 and by impairing sodium excretion by the kidneys. 337 Norepinephrine can also induce cardiac hypertrophy but restrict the ability of the coronary arteries to supply blood to the thickened ventricular wall, leading to myocardial ischemia. 316,338,339 Activation of the sympathetic nervous system can also provoke arrhythmias by increasing the automaticity of cardiac cells, increasing triggered activity in the heart, and promoting the development of hypokalemia.…”

ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult

“…Whereas cardiac adrenergic drive initially supports the performance of the failing heart, long-term activation of the sympathetic nervous system exerts deleterious effects that can be antagonized by the use of beta-blockers. Sympathetic activation can increase ventricular volumes and pressure by causing peripheral vasoconstriction (247) and by impairing sodium excretion by the kidneys (248). Norepinephrine can also induce cardiac hypertrophy but restrict the ability of the coronary arteries to supply blood to the thickened ventricular wall, leading to myocardial ischemia (215,249,250).…”

“…Finally, by stimulating growth and oxidative stress in terminally differentiated cells, norepinephrine can trigger programmed cell death or apoptosis (254). These deleterious effects are mediated through actions on alpha-1-, beta-1-, and beta-2-adrenergic receptors (138,215,(247)(248)(249)(250)(251)(252)(253)(254).…”

α 1 - and α 2 -Adrenoceptor Control of Sodium Transport Reverses in Developing Hypertension

“…5,34,35 SHR excrete significantly less sodium during the onset of hypertension (weeks 4 to 7). 36 As hypertension progresses, the tendency to retain sodium is reversed until levels approximate those of normotensives during weeks 10 to 13.…”