Although preglomerular vascular smooth muscle cells are endowed with Ca2+-activated K+ channels (KCa channels), little is known about the capacity of these channels to influence renal arteriolar resistance and responsive ness to depolarizing agonists. Therefore, experiments were performed to evaluate the hypothesis that opening of KCa channels can promote afferent arteriolar vasodilation and attenuate vasoconstrictor responses to angio tensin II (AngII). The effects of the synthetic KCa channel opener, NS1619, on afferent arteriolar function were assessed videometrically using the in vitro biood-perfused juxtamedullary nephron technique. NS1619 (10-300 μM) evoked concentration-dependent increases in afferent arteriolar lumen diameter which were almost entirely absent when the kidney donor had been pre-treated with the angiotensin-converting enzyme (ACE) inhibitor, enalaprilat (2 mg). In 6 untreated kidneys, 300 μM NS1619 increased afferent diameter by 30 ± 4%, while this same concentration of the KCa channel opener did not significantly alter arteriolar diameter (108 ± 5% of baseline) in 6 enalaprilat-treated kidneys. In a second group of enalaprilat-treated kidneys, exogenous AngII (1 and 10 nM) elicited concentration-dependent reductions in afferent arteriolar diameter which were blunted by 30 μM NS1619. Accordingly, 10 nM AngII decreased afferent diameter by 39 ± 7% before and 22 ± 5% during exposure to the KCa channel opener (p<0.05). In summary, NS1619 was capable of dilating afferent arterioles, but this effect was not evident during ACE inhibition (which reduces endogenous AngII formation). Moreover, this agent suppressed arteriolar vasoconstrictor responsiveness to exogenous AngII. These observations support the contention that opening of KCa channels can influence afferent arteriolar function by modulating the vasoconstrictor influence of AngII.
|Original language||English (US)|
|State||Published - 1997|
ASJC Scopus subject areas
- Molecular Biology