α-Adrenoceptor Modulation of Norepinephrine and ATP Release in Isolated Kidneys of Spontaneously Hypertensive Rats

Abstract

The present study investigates sympathetic cotransmission and its alpha-adrenoceptor-mediated modulation in kidneys of spontaneously hypertensive rats (SHR, 12 to 14 weeks) and age-matched normotensive Wistar-Kyoto rats (WKY). In the presence of cocaine and corticosterone, renal nerve stimulation at 1 Hz (30 seconds) induced a greater outflow of norepinephrine in SHR (4.2 +/- 0.2 pmol/g kidney) than in WKY (3.0 +/- 0.2 pmol/g kidney). The alpha 2-adrenoceptor antagonist rauwolscine (0.01 to 1 mumol/L) increased the stimulation-induced norepinephrine outflow to a greater extent in SHR than in WKY. In contrast, the alpha 1-adrenoceptor antagonist prazosin (0.03 to 3 mumol/L) increased the stimulation-induced norepinephrine outflow to a greater extent in WKY than in SHR. This difference was not observed in the presence of the P1-purinoceptor antagonist 8-(p-sulfophenyl)theophylline (100 mumol/L). Stimulation at 4 Hz (30 seconds) induced an outflow of ATP (SHR, 12.7 +/- 3.3 pmol/g kidney; WKY, 16.7 +/- 2.1 pmol/g kidney; perfusion solution without cocaine and corticosterone). Prazosin (0.03 mumol/L) markedly reduced pressor responses to stimulation and inhibited the induced ATP outflow by 60% to 70%. When prazosin (0.03 mumol/L) was present, rauwolscine (0.1 mumol/L) increased the induced outflow of norepinephrine and ATP and markedly enhanced prazosin-resistant pressor responses. These pressor responses were abolished by the P2-purinoceptor antagonist suramin (300 mumol/L). The results demonstrate an increased alpha 2-adrenoceptor-mediated automodulation of norepinephrine release in SHR kidneys caused by increased intrasynaptic norepinephrine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of Blood Pressure and Obesity With the Dopamine D2 Receptor Gene Taq I Polymorphism

“…39 Negative feedback systems should modulate this hyperactivity through the stimulation of presynaptic ␣ 2 -adrenergic and DD2 receptors. 12,42 In the spontaneously hypertensive rat (SHR), the *Gender was eliminated as an independent predictive factor for SBP. †Age was eliminated as a independent predictive factor for both SFT measurements.…”

“…42 However, the ability of dopamine to stimulate the DD2R and hence inhibit the release of norepinephrine has been shown to be impaired, 43 leading to increased norepinephrine-mediated vasoconstriction. Furthermore, the replacement of a section of chromosome 8 from the SHR that carries the DD2R gene with that from the normotensive Brown-Norway rat reduced blood pressure.…”

Testosterone Effects on Renal Norepinephrine Content and Release in Rats With Different Y Chromosomes

“…43 There is an increased ␣ 2 -adrenoceptor-mediated autoregulation of NE release in SHR kidneys caused by increased intrasynaptic NE. 44 The increase in SNS activity in SHR and SHR/y animals also could be reflected in changes in gene expression that occur through receptor-mediated events involving both NE and its effect on other hormones. It has been proposed that angiotensin II interacts with the SNS to facilitate NE release in the kidney.…”

Relation Between Renal Interstitial ATP Concentrations and Autoregulation-Mediated Changes in Renal Vascular Resistance

“…10 Extracellular ATP exerts a substantial influence on hemodynamic function, acting via P2 purinoceptors, on a variety of tissues and organs, [2][3][4][5] including the kidney. 4,5,[11][12][13][14][15] A growing body of evidence obtained in both dogs and rats supports the hypothesis that extracellular ATP exerts a role in mediating renal autoregulatory vascular resistance responses, 14 -18 which are caused by active adjustments of vascular smooth muscle tone, primarily in the afferent arterioles. 14,15 Studies using the isolated blood-perfused juxtamedullary nephron preparation demonstrated that ATP, superfused over the renal microvessels, exerts selective afferent arteriolar vasoconstriction without affecting efferent arteriolar tone, 19,20 which is an important criterion for the agent mediating autoregulatory behavior.…”