Endothelin in the splanchnic vascular bed of DOCA-salt hypertensive rats.
Vascular capacitance is reduced by endothelin-1 (ET-1) in deoxycorticosterone (DOCA)-salt hypertensive rats. This may contribute to hypertension development. Because the splanchnic blood vessels (especially veins) are important in determining vascular capacitance, we tested the hypothesis that ET-1 levels in the splanchnic vasculature are elevated in hypertensive DOCA-salt compared with normotensive rats. Tissue ET-1 content was measured by ELISA in aorta, vena cava, superior mesenteric artery and vein, and small mesenteric arteries and veins from normotensive sham-operated (sham) and 4-wk DOCA-salt rats. We also determined ET-1 concentration in aortic and portal venous blood (draining the nonhepatic splanchnic organs) in anesthetized and conscious sham and DOCA-salt rats before and after acute blockade of ETB receptor-mediated plasma clearance of ET-1. Results showed a higher ET-1 content in veins than in arteries of similar size. However, ET-1 content was similar in vessels from sham and DOCA-salt rats, except in aorta and superior mesenteric artery, where ET-1 content was greater in DOCA-salt rats. ET-1 concentration was significantly higher in portal venous than in aortic blood, indicating net nonhepatic splanchnic release (nNHSR) of ET-1. However, nNHSR of ET-1 was similar in sham and DOCA-salt rats. Although nNHSR of ET-1 increased significantly after ETB receptor blockade in sham rats, it was completely unchanged in DOCA-salt rats. These data suggest that, despite the absence of ETB receptor-mediated plasma clearance of ET-1, neither the venous peptide content nor the net release of ET-1 is increased in the splanchnic vasculature of DOCA-salt rats. These results argue against the hypothesis that increased venomotor tone in DOCA-salt hypertension is caused by increased ET-1 concentration around splanchnic venous smooth muscle cells.
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824, USA.
Hong
H
Wang
Alex F
AF
Chen
Stephanie W
SW
Watts
James J
JJ
Galligan
Gregory D
GD
Fink
D000758:Anesthesia; D000818:Animals; D001011:Aorta; D001794:Blood Pressure; D003243:Consciousness; D003900:Desoxycorticosterone / Q000494:pharmacology; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D008642:Mesenteric Veins / Q000378:metabolism; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000502:physiology*
D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D044023:Receptor, Endothelin B; D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone