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Peptidergic mechanisms influencing the resistance of the gastrointestinal vascular bed of the estuarine crocodile, Crocodylus porosus, were investigated. The gut was perfused in situ via the mesenteric and the celiac arteries, and the effects of different neuropeptides were tested using bolus injections. Effects on vascular resistance were recorded as changes in inflow pressures. Peptides found in sensory neurons [substance P, neurokinin A, and calcitonin gene-related peptide (CGRP)] all caused significant relaxation of the celiac vascular bed, as did vasoactive intestinal polypeptide (VIP), another well-known vasodilator. Except for VIP, the peptides also induced transitory gut contractions. Somatostatin and neuropeptide Y (NPY), which coexist in adrenergic neurons of the C. porosus, induced vasoconstriction in the celiac vascular bed without affecting the gut motility. Galanin caused vasoconstriction and occasionally activated the gut wall. To elucidate direct effects on individual vessels, the different peptides were tested on isolated ring preparations of the mesenteric and celiac arteries. Only CGRP and VIP relaxed the epinephrine-precontracted celiac artery, whereas the effects on the mesenteric artery were variable. Somatostatin and NPY did not affect the resting tonus of these vessels, but somatostatin potentiated the epinephrine-induced contraction of the celiac artery. Immunohistochemistry revealed the existence and localization of the above-mentioned peptides in nerve fibers innervating vessels of different sizes in the gut region. These data support the hypothesis of an important role for neuropeptides in the control of the vascular bed of the gastrointestinal tract in C. porosus.

Kagstrom, J. and S. Holmgren. Calcitonin gene-related peptide (CGRP), but not tachykinins, causes relaxation of small arteries from the rainbow trout gut. Peptides 19(3) 577–584, 1998.—Possible vasoactive effects on small diameter arteries from the rainbow trout gut of calcitonin gene-related peptide (CGRP-chicken) and different fish tachykinins; substance P (SP-trout), neurokinin A (NKA-trout), scyliorhinin I and II (SCY I and SCY II-dogfish), were investigated. CGRP relaxed precontracted arteries with a pD2 value of 8.3 ± 0.2. Relaxation to CGRP 10−8 M was reduced by 86.4 ± 5.2% by the CGRP-1 receptor antagonist CGRP8–37 (10−6 M), but unaffected by NG-nitro- l -arginine (10−4 M), indomethacin (10−6 M) and by removal of the endothelium, suggesting no involvement of nitric oxide, prostaglandins or endothelium-derived factors. A low number of CGRP immunoreactive fibers were present in the arterial wall. The tachykinins (10−12–10−6 M) occasionally contracted the relaxed vessel. No synergistic action of SP on the CGRP-induced response was found. A dense plexus of tachykinin-containing fibers without coexisting CGRP innervated the arterial wall. Tachykinins or CGRP had no effect on small diameter veins, and no such immunoreactivity was found in these vessels. In conclusion, CGRP- and tachykinin-containing fibers innervate trout gut arteries. CGRP probably is vasodilatory, while the function of the tachykinin fibers is unknown.

Small arteries (internal diameter 376 +/- 69 microns) from the proximal intestine region of the rainbow trout were mounted in a myograph apparatus where changes in isometric tension could be recorded. VIP (vasoactive intestinal polypeptide) caused a concentration-dependent relaxation (10(-9)-3 x 10(-7) M) of vessels precontracted with the alpha-adrenoceptor agonist phenylephrine (10(-5) M). The nitric oxide synthase inhibitor L-NAME (10(-4) M) did not affect the VIP-relaxation, neither did the lipoxygenase inhibitor esculetin (10(-5) M). However, the cyclooxygenase inhibitor indomethacin (10(-6) M) shifted the concentration-response curve significantly to the right. The VIP-relaxation was still present after mechanical removal of the endothelium. Sodium nitroprusside (10(-9)-10(-6) M) caused a concentration-dependent relaxation of the precontracted vessel, indicating the presence of soluble guanylate cyclase in the vascular smooth muscle cells. VIP-immunoreactivity was found in varicose nerve fibers in these vessels, but nitric oxide synthase-immunoreactivity could not be demonstrated. These results suggest that in rainbow trout, as in mammals, VIP is an endogenous vasodilating neuropeptide. No endothelium-dependent mechanism seems to be involved, neither is production of nitric oxide. Instead the relaxation is mediated, at least in part, via prostaglandin synthesis.

Tachykinin control of gut blood flow (measured by pulsed Doppler technique), dorsal aortic pressure, and heart rate were studied in unrestrained spiny dogfish Squalus acanthias injected with the elasmobranch tachykinins scyliorhinin I and II (SCY I and SCY II), the trout tachykinins substance P (SP), and neurokinin A (NKA). Effects on somatic vasculature were measured by in vitro perfusion of the isolated tail. SCY I and trout SP produced hypotension due to a general vasodilation. This caused a transient increase in mesenteric blood flow and a prolonged increase in celiac blood flow. SCY II caused an initial hypertension induced by a general vasoconstriction, followed eventually by an elevated flow in both gut arteries due to dilation of the vascular beds. Trout NKA evoked a short-lasting increase in celiac blood flow due to a decrease in vascular resistance, a late decrease in mesenteric flow due to vasoconstriction, and no effect on the somatic vasculature. None of the peptides affected heart rate. The study demonstrates a significant vasoactive function of fish tachykinins in the vascular system of an elasmobranch species and, in addition, the occurrence of tachykinin receptor subtypes. Immunohistochemistry revealed a NKA/SCY II-like peptide in nerve fibers innervating many vessels, including the celiac and the mesenteric arteries, the gastrointestinal canal, and the heart.

The role of trout substance P (tSP) and neurokinin A (tNKA) in cardiovascular regulation was investigated in the rainbow trout, Oncorhynchus mykiss, in vivo and in vitro. In vivo, the coeliac arterial and ventral aortic relative blood flows were measured with Doppler flow probes, and blood pressure was measured via a cannula inserted into the dorsal aorta. tSP (0.1 and 1 nmol kg−1) and tNKA (1 nmol kg−1) increased both systemic and coeliac vascular resistances, leading to hypertension and bradycardia. In addition, cardiac output was decreased. The mammalian NK1 tachykinin receptor antagonist CP-96,345 did not affect the responses to tSP or tNKA. In vitro perfusions of the dorsal aortic and coeliacomesenteric vascular beds were performed using peristaltic pumps. The dorsal aortic vascular resistance was dose-dependently increased following infusion of the two peptides (pD2 values 7.6 ± 0.1 and 7.3 ± 0.1 for tSP and tNKA, respectively). Tetrodotoxin did not affect the tSP-induced hypertension. Increases in coeliac vascular resistance caused by tSP was correlated with stomach contractions when measurement of intragastric pressure was made using an inserted baloon. In conclusion, native SP and NKA are potent vasoconstrictors of rainbow trout vasculature, a property quite unusual to tachykinins compared with the vasodilation normally seen in mammals.

Changes in cardiac output, heart rate, dorsal aortic blood pressure and coeliac artery blood flow were measured in unrestrained rainbow trout, Oncorhynchus mykiss, following injections of the elasmobranch tachykinins scyliorhinin I and II. The resistance in the coeliac vascular bed and the total systemic vasculature were calculated from blood pressure and flow. In addition, isolated tails were perfused to investigate the effect of the peptides on the somatic vasculature. Scyliorhinin I (SCY I) produced a biphasic change in the coeliac vascular resistance: an initial decrease was followed by an increase. The decrease in coeliac vascular resistance was accompanied by a decrease in the total systemic vascular resistance, leading to an increased cardiac output. The ensuing increase in coeliac vascular resistance caused a slight increase in blood pressure. In the perfused tail, SCY I produced a marked increase in the somatic vascular resistance. Scyliorhinin II (SCY II) decreased the systemic vascular resistance, causing an increase in cardiac output. SCY II also caused a late increase in the coeliac vascular resistance, which led to hypertension and bradycardia. In vitro, SCY II produced a biphasic response in which an initial decrease in the somatic resistance was followed by a larger increase. The results demonstrate that exogenous SCY I and II are vasoactive peptides that act by different mechanisms in the rainbow trout cardiovascular system. Their actions also differ from the actions of substance P previously observed in the cod, Gadus morhua, and possibly involve a neural reflex.