PT - JOURNAL ARTICLE AU - Schmitt, S L AU - Taylor, K AU - Schmidt, R AU - Van Orden, D AU - Williamson, H E TI - The role of volume depletion, antidiuretic hormone and angiotensin II in the furosemide-induced decrease in mesenteric conductance in the dog. DP - 1981 Nov 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 407--414 VI - 219 IP - 2 4099 - http://jpet.aspetjournals.org/content/219/2/407.short 4100 - http://jpet.aspetjournals.org/content/219/2/407.full SO - J Pharmacol Exp Ther1981 Nov 01; 219 AB - Furosemide caused a significant reduction in mesenteric blood flow and conductance as early as 10 min after administration. When fluid losses were not replaced, conductance continued to decline. In volume-repleted animals, conductance fell initially but failed to decrease further. Thus, furosemide decreases mesenteric conductance in two ways: a small early decrease which is not related to volume loss and a later more marked decrease which is related to volume loss. The initial decrease in conductance seen in furosemide-treated animals appears to be mediated via the renin-angiotensin system. In volume-repleted as well as volume-depleted animals, the plasma concentrations of renin and angiotensin II, but not antidiuretic hormone, were increased 10 min after furosemide administration. Also, inhibitors of the renin-angiotensin system abolished the response. The later decrease in mesenteric conductance induced by furosemide is more complex. When fluid losses were not replaced, plasma levels of angiotensin II and renin, as well as antidiuretic hormone, were increased 40 min after furosemide administration. Neither an infusion of Sar1-Ile8-angiotensin II nor hypophysectomy, alone, prevented the furosemide-induced decrease in conductance. The decrease in conductance was reversed when Sar1-Ile8-angiotensin II was infused into hypophysectomized dogs. Thus, the later more marked decrease in conductance induced by furosemide is related to three factors: volume loss, plasma concentration of angiotensin II and plasma concentration of antidiuretic hormone. Mesenteric conductance is decreased by furosemide if plasma concentrations of one or both vasoactive factor are elevated in the presence of a decrease in extracellular volume.