Hemodynamic effects of levcromakalim in neonatal porcine pulmonary hypertension.
Levcromakalim (LKM; a K(ATP) channel opener) reverses hypoxic pulmonary vasoconstriction in isolated pulmonary arteries and perfused lungs. This vasorelaxation is blocked by glibenclamide (GLB; a K(ATP) channel blocker). We evaluated the hemodynamic effect of LKM followed by GLB in a chronically instrumented neonatal porcine model of pulmonary hypertension, created by exposing piglets to hypoxia (n = 7) or heat-killed group B streptococci (GBS) (n = 6). Hypoxia increased pulmonary arterial pressure (PAP), which LKM decreased, and GLB subsequently increased in a dose-dependent manner. Systemic arterial pressure (SAP) did not change with hypoxia but was also decreased by LKM and increased by GLB. GBS also led to increased PAP, but LKM significantly reduced only SAP, which was then increased by GLB. We conclude LKM is capable of reversing hypoxic, but not GBS-induced, pulmonary hypertension but lacks specificity for the neonatal pulmonary vasculature.
Ambalavanan
N
N
Department of Pediatrics, University of Alabama at Birmingham, 35233, USA. ambal@sprynet.com
Bulger
A
A
Ware
J
J
Philips
J
J
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D019806:Cromakalim / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000860:Hypoxia; D015640:Ion Channel Gating / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D013292:Streptococcus agalactiae; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use*
D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D005905:Glyburide