Renal vascular hyperresponsiveness to elevated ionized calcium in spontaneously hypertensive rat kidneys

Abstract

Objectives: Calcium may be indicated in critically ill patients for hemodynamic support. Its well-known action includes peripheral vasoconstriction. Vascular effects of calcium are unknown, however, in the presence of hypertension or in combination with calcium channel blocking drugs, commonly prescribed in the treatment of hypertension. The renal vessels of the spontaneously hypertensive rat (SHR) represent a suitable study model, because their vascular reactivity closely agrees with that in hypertensive humans. The present study should clarify (a) are the renal vessels of SHR responsive to high and low ionized calcium ([Ca++] within the clinical ranges? (b) because release of nitric oxide is calcium ion dependent, are renal vascular responses altered after inhibition of NO synthase? (c) are vascular responses of SHR to hypercalcemia altered by the calcium channel blocking drug verapamil? Animals and interventions: We compared isolated kidneys of SHR and those of two strains of age-matched normotensive rats (NTR) in their responses to high and low [Ca++]. They were perfused with oxygenated, warmed (37 °C) albumin containing Krebs-Henseleit buffer. In protocol A (n = 8 for each rat strain) steady state high [Ca++] (1.88 mmol/l) and low [Ca++] (0.55 mmol/l) were instituted in randomized order. In protocol B (n = 8 for each rat strain) interventions identical to those of protocol A were instituted after inhibition of NO synthase with N^G monomethyl-L-arginine (L-NMMA). In protocol C, high and low [Ca++] levels were instituted in SHR after verapamil pretreatment. At each [Ca++] we measured changes in renal flow at constant perfusion pressures of 100 and 150 mm Hg. Results: In SHR (perfusion pressure 100 mm Hg), high [Ca++] induced a decrease in renal flow (–11.8 ± 1.8 % of control), which was significantly greater (p < 0.05) than the change (− 6.1 ± 1.5 and − 6.9 ± 1.4 % of control) recorded in the two normotensive strains. In SHR (perfusion pressure 150 mmHg), high [Ca++] induced a decrease in renal flow (− 12 ± 1.3 % of control), also significantly greater (p < 0.05) than the changes (− 6.2 ± 1.1 and −5.8 ± 1.7 % of control) in the two normotensive strains. Similar differences and significances were again observed after L-NMMA pretreatment. In SHR, verapamil prevented renal vascular responses in SHR to both high and low [Ca++]. Conclusions: First, renal vascular responses to high [Ca++] in SHR are exaggerated. At the upper end of the hypercalcemia range the observed changes in renal flow at constant perfusion pressure were modest, however, and with lesser degrees of hypercalcemia they may be anticipated to be even less pronounced. Second, effects of high [Ca++] were abolished after verapamil. If these findings are clinically applicable, they are of interest when calcium is infused in patients with hypertension.