Hypothalamic Na+,K(+)-ATPase inhibitor constricts pulmonary arteries of spontaneously hypertensive rats.
Hypothalamic inhibitory factor (HIF) is an endogenous high-affinity inhibitor of Na+,K(+)-ATPase with ouabain-like properties and has been implicated in the pathogenesis of genetic systemic hypertension. We wondered whether HIF might also be associated with the recently demonstrated pulmonary hypertension of spontaneously hypertensive rats (SHRs). We compared HIF effects on the contractility of isolated 2- to 3-mm pulmonary artery (PA) rings from SHRs and age-matched normotensive Sprague-Dawley (SD) rats. HIF caused a reversible, concentration-dependent increase in tension in PA rings of SHR and SD rats, whereas ouabain did not. PA tension development with HIF (4 nM final concentration) was significantly higher in SHRs than in SD rats: 308 +/- 56 mg (mean +/- SE) vs. 137 +/- 26, respectively, p < 0.05. Abdominal aortic contractions induced by HIF did not differ between SHRs and SD rats. In SHRs, but not SD rats, the effect on PA rings was significantly greater than on aortic rings. In all cases, contraction was abolished by phentolamine but was unaffected by calcium-channel blockade using verapamil. HIF-induced tension development required external Ca2+. We conclude that PA rings from SHRs are more sensitive to Na+,K(+)-ATPase inhibitory effects of HIF than PA rings from SD rats, which may contribute to the observed pulmonary hypertension in SHR. Local modulation of the Na+,K(+)-ATPase-adrenergic neuroeffector interaction may be the vasoconstrictive mechanism of action of HIF in these vessels.
Janssens
S P
SP
Pulmonary/Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston.
Kachoris
C
C
Parker
W L
WL
Hales
C A
CA
Haupert
G T
GT
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000503:physiopathology*; D007031:Hypothalamus / Q000737:chemistry*; D066298:In Vitro Techniques; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
C083016:sodium-potassium ATPase inhibitory factor; D010042:Ouabain; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; D010646:Phentolamine