Postnatal changes in gut hemodynamics: a possible role for substance P.
Studies were conducted in young postnatal swine to determine if substance P (SP) participates in the regulation of postnatal intestinal hemodynamics and oxygenation. SP was present in homogenates of whole intestine from postnatal swine in an age-dependent manner as follows: 1 day old and never fed, 126 +/- 35; 3 days old and fasted, 148 +/- 30; and 14 days old, 51 +/- 10 pg/mg protein (P < 0.01, 14- vs. 1- or 3-day-olds). Phenylephrine-precontracted rings of mesenteric artery from 3-day-old subjects mounted for tension recording within buffer-filled myographs demonstrated brisk relaxation in response to SP (EC50, 2 x 10(-10) M). This relaxation was eliminated by mechanical removal of the endothelium or blockade with the L-arginine analog NG-monomethyl-L-arginine (L-NMMA) and was significantly attenuated by pretreatment with N-acyl-L-Trp-3,5-bis-(trifluoromethyl) benzyl ester (NATB), a highly selective NK-1 receptor antagonist (pA2 5 x 10(-10) M). Infusion of exogenous SP into the mesenteric artery of innervated in vivo gut loops reduced intestinal vascular resistance 35% and increased tissue oxygen uptake 40% in both 3- and 14-day-old subjects. By contrast, blockade of the NK-1 receptor for SP with NATB increased intestinal vascular resistance 19% in 3-day-old subjects but only 5% in 14-day-old subjects (P < 0.01). SP-induced changes in gut vascular resistance were significantly attenuated by prior coinfusion of NATB or L-NMMA, indicating that the peptide exerted this vascular effect via theNK-1 receptor, which is linked to endothelial cell nitric oxide synthase. Both NATB and L-NMMA attenuated flow-induced dilation within pump-perfused in vitro gut loops from 3-day-old subjects. SP appears to participate in the regulation of the newborn intestinal circulation, especially during the first days after birth.
Department of Pediatrics, Ohio State University, Columbus, Ohio 43210, USA.
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Nowicki
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics; D007422:Intestines / Q000098:blood supply* / Q000254:growth & development*; D007700:Kinetics; D008638:Mesenteric Arteries / Q000294:innervation / Q000502:physiology; D009121:Muscle Denervation; D009126:Muscle Relaxation / Q000187:drug effects; D064729:Neurokinin-1 Receptor Antagonists; D010101:Oxygen Consumption; D013373:Substance P / Q000494:pharmacology / Q000502:physiology*; D013552:Swine; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D064729:Neurokinin-1 Receptor Antagonists; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; D019323:omega-N-Methylarginine; D013373:Substance P; D014364:Tryptophan