Role of endothelin-1 in regulation of the postnatal intestinal circulation.
Newborn intestine is uniquely prone to vasoconstriction in response to a wide variety of perturbations. To test the hypothesis that endothelin (ET)-1 is an important factor in this process, we determined the effects of exogenous ET-1 administration and blockade of endogenous ET-1 in vivo and in vitro in 3- and 35-day-old swine. Intramesenteric artery administration of exogenous ET-1 to vascularly isolated in vivo gut loops (10(-9) M/kg bolus) caused vasoconstriction and reduced gut O(2) uptake similarly in these age groups. Selective blockade of ET(A) or ET(B) receptors with BQ-610 or BQ-788, respectively, in vascularly isolated in vivo gut loops had no effect on gut vascular resistance or O(2) uptake in either age group; within in vitro gut loops, BQ-610 significantly increased vasoconstriction when perfusion pressure was reduced below baseline, but only in 3-day-old animals; i.e., it impaired the autoregulatory response to perfusion pressure reduction. Exogenous ET-1 significantly decreased capillary perfusion within in vitro gut loops, as evidenced by a decrease in capillary filtration coefficient, but only in 3-day-old animals; furthermore, blockade of endogenous ET-1 activity with BQ-610 significantly enhanced capillary filtration coefficient in 3-day-old animals and increased O(2) extraction ratio. ET-1 did not depress intestinal metabolic rate, as evidenced by its effect on the O(2) uptake-blood flow relationship; it did compromise tissue oxygenation because of its effects on intestinal O(2) transport. ET-1 concentration in mesenteric venous effluent exceeded arterial concentration, but only in 3-day-old intestine, suggesting production of ET-1 by newborn intestine. We conclude that ET-1 exerts an age-dependent effect on intestinal hemodynamics in postnatal intestine, having a greater impact in 3- than in 35-day-old intestine.
Nankervis
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CA
Department of Pediatrics, College of Medicine and Public Health, The Ohio State University and Children's Research Institute, Columbus, Ohio 43205, USA. NankervisC@pediatrics.ohio-state.edu
Nowicki
P T
PT
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D001808:Blood Vessels / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D007269:Injections, Intra-Arterial; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D008638:Mesenteric Arteries; D009842:Oligopeptides / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D012039:Regional Blood Flow / Q000502:physiology; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction; D014886:Weaning
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; C087220:BQ 610; C086539:BQ 788