Renal thromboxane A2 synthesis in the Lyon hypertensive rat.
The aim of the present study was to assess the mechanisms by which norepinephrine (NE) increased the synthesis of prostanoids and revealed a hyperactivity of the Thromboxane (Tx) A2 synthase in the Lyon genetically hypertensive (LH) rat kidney. To this purpose, the effects of NE (1.2 x 10(-8) to 9.6 x 10(-7) M) on renal function and prostanoid synthesis were assessed in isolated perfused kidneys following beta-adrenoceptor blockade by sotalol (10(-5)M) and compared to those of equipressor concentration of an alpha 2-adrenoceptor agonist, BHT 933 (3.5 x 10(-4) M) and angiotensin II (AII) (7.7 x 10(-9) M). Kidneys were isolated from eight week-old male LH rats and from their normotensive (LN) and low blood pressure (LL) controls and perfused in a single pass system. In baseline conditions, sotalol did not modify renal function or urinary prostanoids in any of the three strains. Following NE stimulation, it potentiated the increase in renal vascular resistance of LL and LN controls but not that of LH rats. The pressure-natriuresis and the urinary prostanoids remained unchanged. BHT 933 elicited a weak stimulation of prostanoid release while AII markedly increased it and revealed, as did NE, the hyperactivity of the TxA2 synthase. It is concluded that the NE-induced stimulation of prostanoid synthesis does not involve beta-adrenoceptors and is unrelated to the associated hemodynamic changes. These results also demonstrate that the increased renal synthesis of TxA2 observed in LH rat kidney is not a specific response to alpha-adrenoceptor stimulation and is likely to involve activation of the phosphoinositide pathway.
Department of Physiology and Clinical Pharmacology, URA CNRS 1483, Faculty of Pharmacy, Lyon, France.
K L
KL
Liu
A H
AH
Aissa
D
D
Benzoni
J
J
Sassard
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D013928:Thromboxane A2 / Q000096:biosynthesis*
D000319:Adrenergic beta-Antagonists; D013928:Thromboxane A2; D009638:Norepinephrine