Kvam F I, Ofstad J, Iversen B M
Renal Research Group, Medical Department A, University of Bergen, N-5021 Bergen, Norway.
Am J Physiol. 1998 Oct;275(4):F576-84. doi: 10.1152/ajprenal.1998.275.4.F576.
The relationship between systemic blood pressure and glomerular capillary pressure (Pgc) in spontaneously hypertensive rats (SHR) during treatment with antihypertensive drugs is still unclear. The effects of an angiotensin-converting enzyme inhibitor (enalapril), two calcium channel antagonists (nifedipine and verapamil), and an alpha1-receptor blocker (doxazosin) on renal blood flow (RBF) autoregulation, Pgc, and renal segmental resistances were therefore studied in SHR. Recordings of RBF autoregulation were done before and 30 min after intravenous infusion of the different drugs, and Pgc was thereafter measured with the stop-flow technique. When the mean arterial pressure (MAP) was reduced to approximately 120 mmHg by infusions of doxazosin or enalapril, the lower pressure limit of RBF autoregulation was reduced significantly. Nifedipine or verapamil abolished RBF autoregulation. Doxazosin did not change Pgc (43.6 +/- 1.4 vs. 46.7 +/- 1.5 mmHg in controls, P > 0.5), enalapril lowered (41.3 +/- 0.8 mmHg, P < 0.01), and the calcium channel antagonists increased Pgc [53.7 +/- 1.4 mmHg (nifedipine) and 54.8 +/- 1.2 mmHg (verapamil), P < 0.01]. When MAP was reduced to approximately 85 mmHg by drugs, Pgc was reduced to 43.3 +/- 1.7 mmHg after nifedipine (P > 0.2 vs. control), whereas Pgc after enalapril was 38.5 +/- 0.5 mmHg (P < 0.05 vs. control). Enalapril reduced Pgc mainly by reducing efferent resistance. During treatment with calcium channel antagonists, Pgc became strictly dependent on MAP. Monotherapy with nifedipine may increase Pgc and by this mechanism accelerate glomerulosclerosis if a strict blood pressure control is not obtained.
自发性高血压大鼠（SHR）在使用抗高血压药物治疗期间，体循环血压与肾小球毛细血管压力（Pgc）之间的关系仍不明确。因此，研究了血管紧张素转换酶抑制剂（依那普利）、两种钙通道拮抗剂（硝苯地平和维拉帕米）以及α1受体阻滞剂（多沙唑嗪）对SHR肾血流量（RBF）自动调节、Pgc和肾段阻力的影响。在静脉输注不同药物前和输注后30分钟记录RBF自动调节情况，然后用停流技术测量Pgc。当通过输注多沙唑嗪或依那普利将平均动脉压（MAP）降至约120 mmHg时，RBF自动调节的下限显著降低。硝苯地平或维拉帕米消除了RBF自动调节。多沙唑嗪未改变Pgc（对照组为43.6±1.4 mmHg，用药后为46.7±1.5 mmHg，P>0.5），依那普利使其降低（41.3±0.8 mmHg，P<0.01），而钙通道拮抗剂使其升高[硝苯地平为53.7±1.4 mmHg，维拉帕米为54.8±1.2 mmHg，P<0.01]。当通过药物将MAP降至约85 mmHg时，硝苯地平用药后Pgc降至43.3±1.7 mmHg（与对照组相比，P>0.2），而依那普利用药后Pgc为38.5±0.5 mmHg（与对照组相比，P<0.05）。依那普利主要通过降低出球阻力来降低Pgc。在用钙通道拮抗剂治疗期间，Pgc变得严格依赖于MAP。如果不能严格控制血压，硝苯地平单药治疗可能会升高Pgc，并通过这种机制加速肾小球硬化。
