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Renal calcium‐sensing receptors influence renal hemodynamics via nitric oxide‐mediated vasodilation
Author(s) -
Beierwaltes William H.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.761.6
Subject(s) - cinacalcet , vasodilation , endocrinology , medicine , nitric oxide , chemistry , renal blood flow , vasoconstriction , kidney , calcium , parathyroid hormone , secondary hyperparathyroidism
Calcium (Ca) is a cofactor in both activation of nitric oxide synthase (NOS) and vascular smooth muscle contraction. Both endothelial cells and vascular smooth muscle express Ca‐sensing receptors (CaSR), which increase intracellular Ca in response to increased extracellular Ca. Ca mimetics enhance this signaling. We hypothesized that the Ca mimetic Cinacalcet (Amgen) would cause NO‐mediated renal vasodilation. The effect of Cinacalcet on blood pressure (BP) and renal blood flow (RBF) without and with NOS inhibition by L‐NAME (10 mg/kg bw) were measured in Inaction‐anesthetized male Sprague‐Dawley rats. Without L‐NAME, an i.v. bolus of 30 mg/kg bw Cinacalcet increased BP from 102 ±5 to 112 ±4 mmHg (p<0.001) within 3 min and RBF increased 15% from 6.41 ±0.4 to 7.38 ± 0.4 ml/min/gkw (p<0.001). L‐NAME increased BP by 29 ±4 mmHg and reduced RBF by 45% (p<0.001). Then, Cinacalcet administration produced a similar pressor response as before (11 ±2 mmHg, p<0.01), but now RBF remained unchanged. Thus, we observed the systemic response to activating CaSR was pressor and NO‐independent, but the renal vasodilation was NO‐mediated. We conclude that activating the CaSR does cause NO‐mediated renal vasodilation. This dissociation of systemic and renal responses suggests that in the renal vasculature, CaSR‐activated NOS activity may be a particularly important factor in maintaining renal perfusion.