α1-Adrenoceptors And At1 Receptors In The Modulation Of Renal Hemodynamics In High Salt And Doca Models Of Hypertensive Rats Treated With Tempol And Losartan
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Date
2016-05
Authors
Yong, Pei Pei
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Abstract
Hypertension is a major cause of morbidity and mortality from renal impairment. An increase of sodium intake contributes to the pathogenesis of hypertension. α1-adrenoceptors modulate renal vascular tone in the regulation of blood pressure. This study was undertaken to investigate the effects of tempol and losartan on renal function and haemodynamics in Sprague Dawley (SD) rats fed with normal diet, SD rats fed with high sodium diet, DOCA-salt treated rats fed with normal diet and DOCA-salt treated rats fed with high sodium diet. All models were divided into groups of control, tempol (3mmol/l), losartan (10mg/kg, last 7 days) and combination of tempol and losartan. The animals were studied for 42 days. The acute renal hemodynamic study was performed on day 43. Metabolic data, blood pressure (BP), pulse wave velocity (PWV) and renal vascular responsiveness to noradrenaline (NA), phenylephrine (PE), methoxamine (ME) and angiotensin II (Ang II) were investigated. Data, mean ± SEM were analyzed using one/two-way ANOVA with significance level of 5%. Tempol and losartan did not influence renal function and renal vasculature responsiveness in SD rats fed with normal diet. SD rats given with high sodium diet showed higher BP and renal impairment as evidenced by increased plasma creatinine, creatinine clearance and decreased urinary sodium to potassium ratio. DOCA-salt rats fed with high sodium diet had higher BP and in renal function compromised as supported by increased plasma creatinine, decreased creatinine
clearance and increased fractional sodium excretion. Tempol decreased BP of SD rats fed with high sodium diet, DOCA-salt treated rats fed with normal diet and DOCA-salt treated rats fed with high sodium diet. Similarly, losartan reduced BP in SD rats fed with high sodium diet. High sodium diet decreased the responsiveness of renal α1-adrenoceptors in SD rats fed with high sodium diet and DOCA-salt rats fed with high sodium diet as supported by decreased renal cortical blood perfusion (RCBP) in response to adrenergic agonists. High sodium diet also decreased sensitivity of AT1-receptors in SD rats fed with high sodium diet. Tempol increased % drop of RCBP in response to adrenergic agonists in SD rats fed with high sodium diet. Similarly, losartan increased the responsiveness of α1-adrenergic receptors and decreased the sensitivity of AT1-receptors in DOCA-salt rats fed with high sodium diet. Tempol and losartan given in combination increased % drop of RCBP in response to adrenergic agonists in SD rats fed with high sodium diet and DOCA-salt rats fed with normal diet. Collectively, the results suggest that tempol lowers MAP and improves sensitivity of α1-adrenoceptors thus providing protection against ROS in these hypertensive rat models.
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The effects of tempol and losartan , on renal function and haemodynamics.