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  • Title: Effect of a calcium antagonist on renal hemodynamics in salt-loaded spontaneously hypertensive rats.
    Author: Shimosawa T, Ando K, Fujita T.
    Journal: Jpn Heart J; 1995 Nov; 36(6):797-805. PubMed ID: 8627985.
    Abstract:
    In the present study, we investigated the change in renal hemodynamics induced by a calcium antagonist in young (6 week-old) spontaneously hypertensive rats (SHR), a salt-sensitive hypertensive model. In acute experiments, SHR were fed either a 0.66% or 8.0% NaCl diet for 4 weeks. In acute experiments, manidipine, a calcium antagonist, was administered in a bolus dose of 10 microg/kg. In chronic experiments, SHR were fed a 0.66% NaCl, 0.66% NaCl plus 0.05% manidipine, 8.0% NaCl or 8.0% NaCl plus 0.05% manidipine diet for 4 weeks. Mean arterial pressure (MAP), glomerular filtration rate (GFR), and renal blood flow (RBF) were measured. Salt loading increased MAP in young SHR. Acute administration of manidipine decreased MAP more in salt-loaded SHR compared to non-salt-loaded SHR (-43.3 +/- 3.1 vs. -18.6 +/- 2.1 mmHg: p < 0.01). Moreover, chronic administration of manidipine attenuated the rise in MAP in salt-loaded SHR (155 +/- 3 mmHg vs. 196 +/- 5 mmHg; p < 0.01) and less so in non-salt-loaded SHR (150 +/-2 mmHg vs. 160 +/- 3 mmHg; p < 0.01). Salt loading elevated renal vascular resistance (RVR) but changed neither RBF nor GFR. The acute- and chronic-administration of manidipine increased RBF (Acute; +0.77 +/- 0.22 ml/min/g kidney: p < 0.05, Chronic; 4.32 +/- 0.29 vs. 5.50 +/- 0.90 ml/min/g kidney: p < 0.01) in non-salt-loaded SHR, which was greater in salt-loaded SHR (Acute; +2.19 +/- 0.52 ml/min/g kidney: p 0.05 vs. non-salt-loaded SHR, Chronic; 4.29 +/- 0.53 vs. 6.09 +/- 1.41 ml/min/g kidney: p < 0.01) Manidipine also decreased RVR (Acute; -10.2 +/- 2.2 mmHg/ml/min/g kidney: p < 0.01, Chronic; 35.3 +/- 1.6 vs. 27.3 +/- 4.1 mmHg/ml/min/g kidney: p < 0.01) in non-salt-loaded SHR, which was greater in salt-loaded SHR (Acute; -21.1 +/- 3.1 mmHg/ml/min/g kidney: p < 0.01 vs. non-salt-loaded SHR, Chronic; 44.9 +/- 2.6 vs. 27.6 +/- 4.1 mmHg/ml/min/g kidney: p < 0.01). GFR did not change significantly following manidipine. It is suggested that the antihypertensive effect of the calcium antagonist, manidipine, was greater in salt-loaded SHR and was accompanied by profound amelioration of the abnormal renal hemodynamics.
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