Vyas S J, Jackson E K
Center for Clinical Pharmacology, University of Pittsburgh Medical Center, Pennsylvania, USA.
J Pharmacol Exp Ther. 1995 May;273(2):768-77.
Renovascular and renal excretory responses to intrarenally infused angiotensin II (Ang II) (1 and 3 ng/min, one dose per rat) were assessed in young (approximately 6 weeks of age) anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats acutely treated with captopril. Urinary excretion of cyclic adenosine monophosphate (cAMP) was also measured in these rats to examine whether Ang II has an enhanced ability to inhibit adenylate cyclase activity in SHR. Ang II (1 ng/min i.r.a.) significantly reduced renal blood flow (RBF) and increased renal vascular resistance (RVR) in SHR but not in WKY rats. At this dose, Ang II produced significant decreases in glomerular filtration rate (GFR), filtration fraction (FF), urine volume (UV) and urinary excretion of sodium (UNaV) and potassium (UkV) in SHR without altering any of these parameters in WKY rats. Ang II at either dose did not cause any increase in systemic blood pressure in either SHR or WKY rats. Ang II (3 ng/min i.r.a.) decreased RBF in both SHR and WKY rats to a similar extent. However, the higher dose of Ang II produced significant decrements in GFR, FF, UV, UNaV and fractional excretion of sodium in SHR but not in WKY rats. Also, Ang II at both the doses significantly decreased urinary cAMP excretion rate in SHR without affecting the same in WKY rats. These data demonstrate that, even during the developmental phase of hypertension, the SHR kidney is more responsive to Ang II as compared with the WKY rat kidney. Also, these results suggest that the ability of Ang II to inhibit renal adenylate cyclase activity in young SHR may be enhanced. The exaggerated renal reactivity to Ang II may be an important determinant of the development of hypertension in SHR.
在麻醉状态下，对急性给予卡托普利治疗的年轻（约6周龄）自发性高血压大鼠（SHR）和Wistar-Kyoto（WKY）大鼠，评估肾血管和肾脏对肾内输注血管紧张素II（Ang II）（1和3 ng/分钟，每只大鼠一剂）的排泄反应。还测量了这些大鼠尿中环磷酸腺苷（cAMP）的排泄量，以检查Ang II是否具有增强的抑制SHR中腺苷酸环化酶活性的能力。Ang II（1 ng/分钟肾内输注）显著降低了SHR的肾血流量（RBF）并增加了肾血管阻力（RVR），但对WKY大鼠没有影响。在此剂量下，Ang II使SHR的肾小球滤过率（GFR）、滤过分数（FF）、尿量（UV）以及钠（UNaV）和钾（UkV）的尿排泄量显著降低，而对WKY大鼠的这些参数没有改变。两种剂量的Ang II均未导致SHR或WKY大鼠的全身血压升高。Ang II（3 ng/分钟肾内输注）使SHR和WKY大鼠的RBF降低程度相似。然而，较高剂量的Ang II使SHR的GFR、FF、UV、UNaV和钠分数排泄量显著降低，但对WKY大鼠没有影响。此外，两种剂量的Ang II均显著降低了SHR的尿cAMP排泄率，而对WKY大鼠没有影响。这些数据表明，即使在高血压的发育阶段，与WKY大鼠肾脏相比，SHR肾脏对Ang II的反应性更高。此外，这些结果表明，Ang II抑制年轻SHR中肾腺苷酸环化酶活性的能力可能增强。对Ang II的过度肾反应性可能是SHR高血压发展的重要决定因素。
