RENAL VASCULAR HYPERRESPONSIVENESS TO ELEVATED IONIZED CALCIUM IN SPONTANEOUSLY HYPERTENSIVE RAT KIDNEYS

Objectives: Calcium may be indicated in critically ill patients for he modynamic support. Its well-known action includes peripheral vasoconst riction. Vascular effects of calcium are unknown, however, in the pres ence of hypertension or in combination with calcium channel blocking d rugs, commonly prescribed in the treatment of hypertension, The renal vessels of the spontaneously hypertensive rat (SHR) represent a suitab le 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 i nhibition of NO synthase? (c) are vascular responses of SHR to hyperca lcemia altered by the calcium channel blocking drug verapamil? Animals and interventions: We compared isolated kidneys of SHR and those of t wo strains of age-matched normotensive rats (NTR) in their responses t o high and low [Ca++]. They were perfused with oxygenated, warmed (37 degrees C) albumin containing Krebs-Henseleit buffer. In protocol A (n = 8 for each rat strain) steady slate high [Ca++] (1.88 mmol/l) and l ow [Ca++] (0.55 mmol/l) were institut- ed in randomized order, In prot ocol B (n = 8 for each rat strain) interventions identical to those of protocol A were instituted after inhibition of NO synthase with N-G m onomethyl-L-arginine (L-NMMA). In protocol C, high and low [Ca++] leve ls were instituted in SHR after verapamil pretreatment. At each [Ca++] we measured changes in renal flow at constant perfusion pressures of 100 and 150 mmHg. Results: In SHR (perfusion pressure 100 mmHg), 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 str ains. In SHR (perfusion pressure 150 mmHg), high [Ca++] induced a decr ease in renal flow (-12 +/- 1.3 % of control), also significantly grea ter (p < 0.05) than the changes (-6.2 +/- 1.1 and -5.8 +/- 1.7 % of co ntrol) in the two normotensive strains. Similar differences and signif icances were again observed after L-NMMA pretreatment. In SHR, verapam il 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 obse rved changes in renal flow at constant perfusion pressure were modest, however, and with lesser degrees of hypercalcemia they may be anticip ated to be even less pronounced, Second, effects of high [Ca++] were a bolished after verapamil. If these findings are clinically applicable, they are of interest when calcium is infused in patients with hyperte nsion.