| Endogenous κ opioid peptides have effects of inhibiting cardiac contraction, decreasing HR(heart rate), and causing vasodilatation in cardiovascular system. It has been found that Endogenous opioid peptides also act on kidney to regulate the formation of urine. Many experiments confirm that exogenous κ opioid receptor agonist like U50,488H induce diuresis significantly in normatensive rats.Humoral regulation is the principal factor in regulation of urinary formation. Experimental data indicate that the decrease in ADH secretion maybe the main mechanism of U50,488H producing diuretic effect. The recent researches showed that the activation of κ opioid receptor induces dose-dependently increasing of ANP' s level in atrial myocytes, plasma and aqueous humor. Accordingly, the contribution of κ opioid receptor agonist to humoral regulation is to attenuate the factors causing the increasing of urine output and to promote the factors causing the decreasing of urine output, which results in diuretic effect.It is less reported whether κ opioid peptides and the activating of κopioid receptor still have strongly diuretic effect in the hypertensive condition and the underlying mechanism. In hypertensive diseases, the activity of the ADH, catecholamine(CAT) and RAAS (renin-angiotensin-aldosterone-system) increase abnormally. It is presumed that κ opioid receptor stimulation inhibits the effects of above humoral factors in the state of hypertensive disease, and then leading to the diuretic effect. The guess warrants further study.The present study uses SHR (spontaneously hypertensive rats) to investigate the effect of κ opioid receptor agonist on the regulation of urinary formation in hypertensive condition and its underlying mechanism. Objective(1) To study the influence of κ opioid receptor agonist on the UV(urinary volume) and blood pressure in WKY and SHR.(2) To observe the effect of κ opioid receptor agonist on renal artery of WKY and SHR.(3) To study the regulating effect of κ opioid receptor agonist on plasma concentration of humoral factors in WKY and SHR.Methods(1) The physiological experimental technique was used to collect the urine and to determine the hemodynamic parameters, and urinary flow rate and volume of urine output.were measured.(2) Isolated artery perfusion technique was used to investigate the direct action of U50,448H on renal artery of WKY and SHR.(3) The RIA (radioimmunoassay) was made use to determine the effects of U50,448H on the plasma level of ADH, ANP and Ang II.Results(1) Normatensive WKY (Wistar-Kyoto) rats and SHR (spontaneously hypertensive rats) were given U50, 448H intravenously in three doses as 0.1 mg/Kg, 0.3 mg/Kg, and 1 mg/Kg. Compared to the corresponding saline group, the urine volume increased dose-dependently in each dose group. At every dose , the urine volume of SHR increased by U50,448H was more than that of normatensive WKY. The significant difference was produced at a dose of 1 mg/Kg (P<0.05) . The diuretic effect of U50,448H was abolished by selective κ opioid receptor antagonist Nor-BNI.(2) When U50,448H at dose of 1 mg/Kg dose was administersed to WKY rats and SHR, MAP (mean arterial pressure) decreased significantly. MAP of WKY rats dropped maximumly after U50,448H administration for 30 min with the decrease rate of (29.6±8.1) %, while that of SHR did after 40 min with the decrease rate of (56.8±4.2) % (P<0.01). This effect of U50,448H in WKY rats and SHR could be inhibited by κ opioid receptor antagonist Nor-BNI (1mg/Kg).(3) U50,488H had a significant dose-dependent relaxant effect on renal artery in WKY rats and SHR, and the maximum relaxant effect of U50,488H in SHR was not different from WKY rats (P>0.05) . The relaxation of U50,488H on renal artery in WKY rats was enhanced with denuded endothelium and the relaxation of U50,488H on renal artery in SHR was not attenuated by endothelium denudation. The relaxant effect of U50,488H on renal artery was not influenced by different blockers such as glibenclamide, L-NAME, indomethacin, atropine, propranalol in WKY rats and SHR.(4) U50,488H (1 mg/Kg) produced marked decrease in plasma concentration of ADH in WKY rats and SHR, and the decrease in SHR was... |
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