Silldorff E P, Kreisberg M S, Pallone T L
Department of Medicine, Division of Nephrology, Pennsylvania State University, Hershey Medical Center, Hershey 17033, USA.
J Clin Invest. 1996 Jul 1;98(1):18-23. doi: 10.1172/JCI118764.
Adenosine is generated within the renal medulla under hypoxic conditions and is known to induce net vasoconstriction within the renal cortex while increasing medullary blood flow and oxygenation. To test the hypothesis that vasoconstriction of outer medullary descending vasa recta (OMDVR) is modulated by adenosine, we examined the effects of adenosine and adenosine Al and A2 receptor subtype agonists on in vitro perfused control and preconstricted rat OMDVR. Constriction with angiotensin II (ANG II, 10(-9) M) was attenuated by adenosine in a concentration-dependent manner (EC50 = 2.0 x 10(-7)M, P < 0.05). Similarly, an adenosine A2 agonist (CGS-21680, 10(-7) M), but not an adenosine Al agonist (cyclohexyladenosine, 10(-6) M), attenuated ANG II-induced vasoconstriction. Under control conditions, ablumenal application of adenosine (10(-12) to 10(-5) M) elicited a biphasic response. Additionally, cyclohexyladenosine (10(-6) M) caused vasoconstriction and CGS-21680 (10(-6) M) had no effect on untreated vessels. Finally, an influence of ANG II receptor stimulation on adenosine Al receptor-mediated vasoconstriction could not be shown. These data suggest that OMDVR possess both Al and A2 adenosine receptors and that they mediate constriction and dilatation, respectively. We conclude that adenosine is a potent modulator of OMDVR vasomotor tone and that its net effect is dependent upon local concentrations.
在缺氧条件下,肾髓质内会生成腺苷,已知其可诱导肾皮质内的净血管收缩,同时增加髓质血流量和氧合作用。为了验证外髓质直小血管降支(OMDVR)的血管收缩受腺苷调节这一假设,我们研究了腺苷、腺苷A1和A2受体亚型激动剂对体外灌注的对照和预收缩大鼠OMDVR的影响。腺苷以浓度依赖性方式减弱血管紧张素II(ANG II,10⁻⁹ M)引起的收缩(EC50 = 2.0 x 10⁻⁷M,P < 0.05)。同样,腺苷A2激动剂(CGS - 21680,10⁻⁷ M)可减弱ANG II诱导的血管收缩,而腺苷A1激动剂(环己基腺苷,10⁻⁶ M)则无此作用。在对照条件下,从管腔外施加腺苷(10⁻¹²至10⁻⁵ M)会引发双相反应。此外,环己基腺苷(10⁻⁶ M)引起血管收缩,而CGS - 21680(10⁻⁶ M)对未处理的血管无影响。最后,未发现ANG II受体刺激对腺苷A1受体介导的血管收缩有影响。这些数据表明,OMDVR同时具有A1和A2腺苷受体,且它们分别介导血管收缩和舒张。我们得出结论,腺苷是OMDVR血管运动张力的有效调节剂,其净效应取决于局部浓度。