Premium
Nebivolol induced vasodilation of renal afferent arterioles involves β3 adrenergic receptor activation
Author(s) -
Feng Ming-Guo,
Navar L. Gabriel
Publication year - 2012
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.26.1_supplement.690.15
Subject(s) - vasodilation , nebivolol , medicine , endocrinology , chemistry , receptor , adrenergic , pharmacology , blood pressure
Nebivolol (Neb) is a novel β1 adrenergic blocker that also elicits vasodilation. However, the renal vasodilator mechanisms remain unclear. Videomicroscopic measurements of vascular dimensions were performed on rat isolated blood perfused juxtamedullary nephrons to test the hypothesis that Neb induced vasodilation of afferent arterioles (AA) involves β3 receptor activation stimulating NOS and NO. Single AA were superfused with Neb either alone or combined with selective β adrenergic blockers: metoprolol (MTP, β1), butoximine (BTX, β2), SR59230A (SR, β3); the sGC inhibitor, ODQ and the NOS inhibitor, L‐NNA. Neb 100μM increased AA diameters by 17.4±2.3% (n=12, p<0.01); however, MTP up to 80μM did not elicit significant changes in AA diameters (1.3±0.7%, n=6) and did not prevent the effects of Neb to dilate AA diameters (15.0±2.5%, n=6, p<0.01). Likewise, BTX failed to block the Neb effect. In contrast, the Neb induced vasodilation was markedly attenuated by SR 5μM (4.9±1.1% vs baseline, n=6, p>0.05). Pretreatment with ODQ 10μM (n=5) or L‐NNA 100μM (n=6) prevented the vasodilation response to Neb. These data indicate that the vasodilator effect of Neb is via a mechanism that is independent of β1 receptors but is predominantly mediated via NOS‐NO‐sGC‐cGMP dependent mechanisms initiated by activation of β3 receptors presumably on AA endothelial cells. (Supported by grant BYSMD62 from Forest Research Institute US)