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.
Nowicki
P T
PT
Department of Pediatrics, Ohio State University, Columbus, Ohio 43210, USA.
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