Renal alpha 2-adrenergic receptors and hypertension.

Pettinger, William A.

doi:10.1161/01.hyp.9.1.3

Cited by 27 publications

(13 citation statements)

References 18 publications

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“…28,29 However, the role of ␣ 2 -receptor stimulation on renal function is clearly quite complex. It has been reported that ␣ 2 -receptor stimulation can produce renal vasoconstriction and inhibit sodium and water excretion, 30 an effect opposite those found in the present study. More consistent with the results of the present study, several genetic hypertensive rat models (spontaneously hypertensive, Dahl salt-sensitive, and Sabra rats) have been reported to exhibit markedly increased density of renal ␣ 2 -receptors, 30 which could represent compensatory changes in response to hypertension.…”

Section: Chronic Antihypertensive Actions Of Medullary No Mediated Bycontrasting

confidence: 99%

Increase in Renal Medullary Nitric Oxide Synthase Activity Protects From Norepinephrine-Induced Hypertension

et al. 2000

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Abstract-Studies were performed in conscious Sprague-Dawley rats to determine the role of the ␣ 2 -adrenergic receptor-mediated increase in the renal medullary nitric oxide synthase (NOS) activity as a counterregulatory mechanism of blood pressure control in response to increased renal adrenergic stimulation. A subpressor dose of norepinephrine (NE, 8 g ⅐ kg Ϫ1 ⅐ h Ϫ1 ) was infused intravenously, and NOS activity was determined with arginine-citrulline conversion by high-performance liquid chromatography in renal cortical and outer and inner medullary tissues. It was found that after 7 days of intravenous NE infusion, NOS activity was significantly higher in both the outer and inner medullary tissues (158Ϯ45 versus 30Ϯ24 pmol ⅐ mg Ϫ1 ⅐ h Ϫ1 [outer medulla] and 5.1Ϯ0.7 versus 2.0Ϯ0.5 nmol ⅐ mg Ϫ1 ⅐ h Ϫ1 [inner medulla] for NE-treated versus control rats, respectively). To determine whether the increase of NOS activity was mediated through renal medullary ␣ 2 -receptors, the receptor antagonist rauwolscine (RAU, 1 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) was infused via an implanted renal medullary interstitial catheter, and the consequences of intravenous NE administration were evaluated. NOS activity was significantly lower in the RAU-infused animals and did not increase with infusion of NE. To determine the systemic effects of the renal medullary ␣ 2 -receptors, studies were performed to determine the consequences of chronic intravenous infusion of subpressor amounts of NE in the presence and absence of renal medullary ␣ 2 -receptor inhibition. Under conditions in which RAU was continuously infused into the renal medulla, the same subpressor dose of NE caused sustained and reversible hypertension (mean arterial pressure increased from 120Ϯ3 to 131Ϯ3 mm Hg). Chronic blunting of the renal medullary NOS activity with N G -nitro-L-arginine methyl ester (75 g ⅐ kg Ϫ1 ⅐ h Ϫ1 ) also enabled NE to produce a significant rise in mean arterial pressure (from 117Ϯ2 to 134Ϯ4 mm Hg). We conclude that the hypertensive effects of moderate elevations of renal adrenergic activity were chronically buffered by the ␣ 2 -receptor-mediated increase in NOS activity within the renal medulla. Key Words: norepinephrine Ⅲ receptors, adrenergic, alpha Ⅲ rauwolscine Ⅲ nitric oxide synthase Ⅲ rats I t has been found that small subpressor amounts of intravenously infused norepinephrine (NE) can stimulate renal medullary nitric oxide concentration ([NO]) in anesthetized Sprague-Dawley rats. 1 This NE-stimulated medullary nitric oxide (NO) release significantly counteracted the medullary vasoconstrictor actions of NE, suggesting an important counterregulatory role of the adrenergic-NO interactions. Sai et al 2 showed that in isolated perfused outer medullary vasa recta, N G -nitro-L-arginine methyl ester (L-NAME) increased the NE response. These observations are of relevance to the longterm control of arterial blood pressure 3 because the renal medullary circulation plays an important role in the mechanism of pressure natriuresis. 4 -7 Chronic reductions of blood ...

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Section: Chronic Antihypertensive Actions Of Medullary No Mediated Bycontrasting

confidence: 99%

Increase in Renal Medullary Nitric Oxide Synthase Activity Protects From Norepinephrine-Induced Hypertension

et al. 2000

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“…They decrease the secretion of vasopressin and antagonise its action on renal tubules [89]. Alpha-2 adrenoceptors are also thought to inhibit the release of renin [90] and increase the release of atrial natriuretic factor [91] in the rat.…”

Section: Cardiovascular System Effectsmentioning

confidence: 99%

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Khan¹,

Ferguson²,

Jones³

1999

Anaesthesia

606

423

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SummaryClonidine has proved to be a clinically useful adjunct in clinical anaesthetic practice as well as in chronic pain therapy because it has both anaesthetic and analgesic-sparing activity. The more selective alpha-2 adrenoceptor agonists, dexmedetomidine and mivazerol, may also have a role in providing haemodynamic stability in patients who are at risk of peri-operative ischaemia. The side-effects of hypotension and bradycardia have limited the routine use of alpha-2 adrenoceptor agonists. Investigations into the molecular pharmacology of alpha-2 adrenoceptors have elucidated their role in the control of wakefulness, blood pressure and antinociception. We discuss the pharmacology of alpha-2 adrenoceptors and their therapeutic role in this review.

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“…High salt feeding (8% NaCI chow) further increases the density of the receptors, paralleled by a rise in blood pressure (5). Based on these results it was assumed that renal a2-adrenoceptor expression is increased in S rats via two distinct but unknown mechanisms: a genetic predisposition for increased renal a2-adrenoceptor expression and an abnormal a2-adrenoceptor upregulation in response to high dietary NaCI (5,25). However, despite the fact that this assumption has been widely cited, it has never been investigated experimentally until the present study.…”

Section: Discussionmentioning

confidence: 92%

Renal .ALPHA.2-Adrenoceptor Overexpression in Dahl Salt-Sensitive Rats. Regulation by Dietary NaCl and Dissociation from Salt-Insensitive Hypertension.

et al. 1992

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Dietary NaCI-induced changes in blood pressure and agonist and antagonist binding properties to renal a2-adrenoceptors were studied in inbred (Rapp) strains of Dahl salt-sensitive (S) and salt-resistant (R) rats. S and R rats were placed on either salt-deficient (0.13% NaCI in chow) or high salt (1% NaCI solution to drink plus 0.13% NaCI chow) diets for 1 to 8 weeks. Saturation binding studies with [3H]-rauwolscine and [H]-p-aminoclonidine and competition studies with [3H]-rauwolscine and epinephrine were then performed in renal plasma membranes from each group. Systolic blood pressure rose significantly in S rats on the salt-deficient diet for 2 or more weeks, and was further increased by high salt intake, indicating that there are salt-sensitive and salt-insensitive components to the hypertension in inbred S rats. The blood pressure of R rats was unaffected by dietary NaCI content. Two or more weeks of high salt feeding significantly elevated renal a2-adrenoceptor density ([3H]-rauwolscine binding) in S but not R rats. Interestingly, NaCI restriction in weanling S rats completely prevented this increase in a2-adrenoceptor density over the course of the study. The number of hih affinity agonist binding sites (assessed with [3H] p-aminoclonidine and epinephrine displacement of [ H]-rauwolscine) was increased in S rats after high salt feeding. Removal of the high salt diet failed to reverse the NaCI-induced elevations in total and high affinity a2-adrenoceptor density in S rats. We conclude that: 1) the initiation of renal a2-adrenoceptor overexpression in Dahl S rats is entirely dependent on dietary NaCI content; 2) the overexpression of renal a2-adrenoceptors was independent of the salt-insensitive component of hypertension in S rats, precluding a causal linkage between these parameters;3) the rise in renal a2-adrenoceptors was closely paralleled by salt-sensitive increments in blood pressure, suggesting a functional relationship between these two variables; 4) In contrast to reported changes in renal a2-adrenoceptor properties following renal denervation, dietary NaCI augments the number of high affinity renal a2-adrenoceptor agonist binding sites in S rats but does not increase the proportion of these sites relative to total receptor number. (Hypertens Res 1992;15: 85-92)

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Renal alpha 2-adrenergic receptors and hypertension.

Cited by 27 publications

References 18 publications

Increase in Renal Medullary Nitric Oxide Synthase Activity Protects From Norepinephrine-Induced Hypertension

Increase in Renal Medullary Nitric Oxide Synthase Activity Protects From Norepinephrine-Induced Hypertension

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Renal .ALPHA.2-Adrenoceptor Overexpression in Dahl Salt-Sensitive Rats. Regulation by Dietary NaCl and Dissociation from Salt-Insensitive Hypertension.

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