Multiple Ca(2+)-dependent modulators mediate alkalosis-induced vasodilation in newborn piglet lungs.
We previously found that alkalosis-induced vasodilation was mediated by endothelium-derived nitric oxide (EDNO) in newborn piglet pulmonary artery and vein rings precontracted with the thromboxane mimetic U-46619. In contrast, prostacyclin or K(+) channel activation contributed to the response in other preparations. This study was undertaken to determine whether EDNO alone also mediates alkalosis-induced pulmonary vasodilation in piglet lungs vasoconstricted with hypoxia and, if not, to identify the mediator(s) involved. Responses to alkalosis were measured during hypoxia under control conditions after blocking nitric oxide synthase (N(omega)-nitro-L-arginine), cyclooxygenase (meclofenamate), or both endothelium-derived modulators (Dual); after blocking voltage-dependent (4-aminopyridine), ATP- dependent (glibenclamide), or Ca(2+)-dependent K(+) (K(Ca); tetraethylammonium) K(+) channels; and after blocking both endothelium-derived modulators and K(Ca) channels (Triple). Vasodilator responses measured after 20 min of alkalosis were blunted in Dual and tetraethylammonium lungs and abolished in Triple lungs. Thus alkalosis-induced vasodilation in hypoxic lungs appeared to be mediated by three Ca(2+)-dependent modulators: EDNO, prostacyclin, and K(Ca) channels. In addition, a transient, unidentified modulator contributed to the nadir of the vasodilator response measured at 10 min of alkalosis. Future studies are needed to identify factors that contribute to the discordance between isolated vessels and whole lungs.
Vander Heyden
M A
MA
Department of Pediatrics, Medical College of Wisconsin and Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin 53226, USA.
Halla
T R
TR
Madden
J A
JA
Gordon
J B
JB
D000471:Alkalosis / Q000503:physiopathology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D002118:Calcium / Q000097:blood / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology*; D009994:Osmolar Concentration; D011652:Pulmonary Circulation / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000502:physiology*
D009569:Nitric Oxide; D002118:Calcium