title: Closure of multiple types of K+ channels is necessary to induce changes in renal vascular resistance in vivo in rats.
abstract: Inhibition of K(+) channels might mediate renal vasoconstriction. As inhibition of a single type of K(+) channel caused minor or no renal vasoconstriction in vivo in rats, we hypothesized that several classes of K(+) channels must be blocked to elicit renal vasoconstriction. We measured renal blood flow (RBF) in vivo in anesthetized Sprague-Dawley rats. Test agents were infused directly into the renal artery to avoid systemic effects. Inhibition of BK(Ca) and K(ir) channels (with TEA and Ba(2+), respectively) caused small and transient reductions in RBF (to 93 ± 2% and 95 ± 1% of baseline, respectively). K(ATP), SK(Ca) or K(v) channel blockade (with glibenclamide, apamin and 4-aminopyridine, respectively) was without effect. However, a cocktail of all blockers caused a massive reduction of RBF (to 15 ± 10% of baseline). Nifedipine and mibefradil abolished and reduced, respectively, this RBF reduction. The effect of the cocktail of K(+) channel blockers was confirmed in mice using the isolated blood-perfused juxtamedullary nephron preparation. A cocktail of K(+) channel openers (K(+), NS309, NS1619 and pinacidil) had only a minor effect on baseline RBF in vivo in rats, but reduced the vasoconstriction induced by bolus injections of norepinephrine or angiotensin II (by 33 ± 5% and 60 ± 5%, respectively). Our results indicate that closure of numerous types of K(+) channels could participate in the mediation of agonist-induced renal vasoconstriction. Our results also suggest that renal vasoconstriction elicited by K(+) channel blockade is mediated by nifedipine-sensitive Ca(2+) channels and partly by mibefradil-sensitive Ca(2+) channels.
authors.affiliation: Department of Biomedical Sciences, Division of Renal and Vascular Physiology, University of Copenhagen, Copenhagen, Denmark. cmehlin@sund.ku.dk
authors.forename: Charlotte Mehlin
authors.initials: CM
authors.lastname: Sorensen
authors.forename: Isaiah
authors.initials: I
authors.lastname: Giese
authors.forename: Thomas Hartig
authors.initials: TH
authors.lastname: Braunstein
authors.forename: Niels-Henrik
authors.initials: NH
authors.lastname: Holstein-Rathlou
authors.forename: Max
authors.initials: M
authors.lastname: Salomonsson
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D020748:Mibefradil / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D001562:Benzimidazoles; D015220:Calcium Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C086491:NS 1619; D020748:Mibefradil; D009543:Nifedipine