HYPOTHALAMIC NA-ATPASE INHIBITOR CONSTRICTS PULMONARY-ARTERIES OF SPONTANEOUSLY HYPERTENSIVE RATS(,K+)

Hypothalamic inhibitory factor (HIF) is an endogenous high-affinity in hibitor of Na+,K+-ATPase with ouabain-like properties and has been imp licated in the pathogenesis of genetic systemic hypertension. We wonde red whether HIF might also be associated with the recently demonstrate d pulmonary hypertension of spontaneously hypertensive rats (SHRs). We compared HIF effects on the contractility of isolated 2- to 3-mm pulm onary artery (PA) rings from SHRs and age-matched normotensive Sprague -Dawley (SD) rats. HIF caused a reversible, concentration-dependent in crease in tension in PA rings of SHR and SD rats, whereas ouabain did not. PA tension development with HIF (4 nM final concentration) was si gnificantly higher in SHRs than in SD rats: 308 +/- 56 mg (mean +/- SE ) vs. 137 +/- 26, respectively, p < 0.05. Abdominal aortic contraction s 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-i nduced tension development required external Ca2+. We conclude that PA rings from SHRs are more sensitive to Na+,K+-ATPase inhibitory effect s of HIF than PA rings from SD rats, which may contribute to the obser ved pulmonary hypertension in SHR. Local modulation of the Na+,K+-ATPa se-adrenergic neuroeffector interaction may be the vasoconstrictive me chanism of action of HIF in these vessels.