Regulation of atrial natriuretic factor receptors in portal hypertensive rabbits

Portal hypertension is characterized by a marked splanchnic hyperemia due to a reduction in mesenteric vascular resistance. Possible mediators of this decreased resistance include an increased amount of and/or responsiveness to vasodilatory substances. Previous studies have demonstrated an enhanced hypotensive effect of exogenous atrial natriuretic factor in portal hypertension. We hypothesized that changes in the atrial natriuretic factor hormone receptor system may contribute to this response and hence underlie the marked hyperemia of portal hypertension. Methods: We used a portal-vein-ligated rabbit model of portal hypertension to study the integrity of the atrial natriuretic factor receptor system within the hyperemic vasculature. Results: There was no significant difference in the serum concentrations of sodium, potassium, atrial natriuretic factor, ANG-II, cGMP, serum osmolality, or hematocrit between normal and portal hypertensive rabbits. Superior mesenteric artery, thoracic aorta and portal vein atrial natriuretic factor receptor number and affinity were determined using [125I]-rANF99–126 binding analysis and affinity cross-linking studies. Receptor classification using specific atrial natriuretic factor-C receptor ligands, along with affinity cross-linking studies revealed two receptor subtypes present on these vessels. There was a significant decrease in the number of atrial natriuretic factor receptors in the portal vein and a significant increase in the superior mesenteric artery in portal hypertension without any significant change in affinity. Thoracic aortic atrial natriuretic factor receptors were increased with a concurrent decrease in affinity in portal hypertension. There was a concomitant increase in tissue cGMP levels within the superior mesenteric artery and thoracic aorta of portal hypertensive animals but not the portal vein. Conclusion: These data suggest the increased number of functional atrial natriuretic factor receptors may in part contribute to the hyperdynamic splanchnic circulation peculiar to portal hypertension.