Villarreal D, Freeman R H, Verburg K M, Brands M W
Department of Physiology, University of Missouri School of Medicine, Columbia.
Proc Soc Exp Biol Med. 1988 Jul;188(3):316-22. doi: 10.3181/00379727-188-42740.
The effects of alpha-rat calcitonin gene-related peptide (alpha-rCGRP) on systemic and renal hemodynamics and on renal electrolyte excretion were examined in normal anesthetized rats. In one group of rats (n = 7), infusions of alpha-rCGRP at doses of 10, 50, 100, and 500 ng/kg/min for 15 min each produced dose-related and significant decreases in mean arterial pressure from a control of 130 +/- 3 mm Hg to a maximal depressor response of 91 +/- 2 mm Hg. During the first three doses of alpha-rCGRP, renal blood flow progressively and significantly increased from a control of 5.0 +/- 0.3 ml/min to a peak level of 6.3 +/- 0.3 ml/min achieved during the 100 ng/kg/min infusion. With the highest infusion rate of 500 ng/kg/min, renal blood flow fell below the control level to 4.5 +/- 0.2 ml/min (P less than 0.05). The responses in renal blood flow and mean arterial pressure were associated with reductions in renal vascular resistance. After cessation of alpha-rCGRP infusions, arterial pressure, renal blood flow, and renal vascular resistance gradually returned toward the baseline values. In another group of rats (n = 9), infusion of alpha-rCGRP for 30 min at 100 ng/kg/min produced a significant reduction in urinary sodium excretion from 0.28 +/- 0.06 to 0.14 +/- 0.5 muEq/min (P less than 0.05). Urine flow and urinary potassium excretion also appeared to decrease, but the changes were not significantly different (P greater than 0.05) from their respective baselines. These results demonstrate that alpha-rCGRP is a potent and reversible hypotensive and renal vasodilatory agent in the anesthetized rat. The data also suggest that alpha-rCGRP may have significant effects on the excretory function of the kidney.
在正常麻醉大鼠中研究了α-大鼠降钙素基因相关肽(α-rCGRP)对全身和肾脏血流动力学以及肾脏电解质排泄的影响。在一组大鼠(n = 7)中,以10、50、100和500 ng/kg/min的剂量输注α-rCGRP,每次输注15分钟,平均动脉压出现剂量相关的显著下降,从对照值130±3 mmHg降至最大降压反应值91±2 mmHg。在前三个α-rCGRP剂量期间,肾血流量从对照值5.0±0.3 ml/min逐渐显著增加至在输注100 ng/kg/min期间达到的峰值水平6.3±0.3 ml/min。在最高输注速率500 ng/kg/min时,肾血流量降至对照水平以下,为4.5±0.2 ml/min(P<0.05)。肾血流量和平均动脉压的反应与肾血管阻力降低有关。停止输注α-rCGRP后,动脉压、肾血流量和肾血管阻力逐渐恢复至基线值。在另一组大鼠(n = 9)中,以100 ng/kg/min的剂量输注α-rCGRP 30分钟,尿钠排泄从0.28±0.06显著降低至0.14±0.5 μEq/min(P<0.05)。尿流量和尿钾排泄也似乎减少,但变化与各自基线相比无显著差异(P>0.05)。这些结果表明,α-rCGRP在麻醉大鼠中是一种强效且可逆的降压和肾血管舒张剂。数据还表明,α-rCGRP可能对肾脏的排泄功能有显著影响。