Mediators of nonadrenergic, noncholinergic (NANC) relaxation in longitudinal muscle of several regions of ICR mouse intestine were studied. An inhibitor of synthesis of nitric oxide, N^G-nitro-L-arginine (L-NOARG) at 10μM significantly inhibited NANC relaxations induced by electrical field stimulation (EFS) in the jejunum, ileum, and the proximal and distal colon. Especially in the ileum extent of the inhibition was more than 80%. An antagonist of vasoactive intestinal peptide (VIP) receptors, VIP_10-28 at 3μM partially inhibited the EFS-induced relaxations in the jejunum and proximal colon, but very slightly in the distal colon and had no effect in the ileum. An antagonist of pituitary adenylate cyclase activating peptide (PACAP) receptor, PACAP_6-38 at 3μM partially inhibited the EFS-induced relaxations in the proximal and distal colon, but not in the jejunum and ileum. Totals of the percentages of relaxant components mediated by nitric oxide, VIP and PACAP in every region are roughly equal to a hundred percent. In another series of experiments, EFS-induced relaxations were almost completely inhibited by the treatment of the segments with L-NOARG and VIP_10-28 in the jejunum, with L-NOARG, VIP 10_28 10-28 and PACAP6-38 in the proximal colon, and with L-NOARG and PACAP_6-38 in the distal colon. The present results suggest that nitric oxide solely mediates the relaxation of longitudinal muscle of the ileum of ICR mice, whereas nitric oxide and VIP co-mediate it in the jejunum, nitric oxide, VIP and PACAP in the proximal colon, and nitric oxide and PACAP in the distal colon.

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Mesenteric arteries were isolated from the spontaneous diabetic BB rats, non-diabetic BB rats and regular Wistar control rats. Gross morphology indicated that the mesenteric vascular bed of the control Wistar rats had a normal development of mesenteric fat pad around the vessels, while that of the diabetic BB rats showed drastically reduced perivascular fat pad, suggesting greater mobilization of fat for energy consumption in the hyperglycemic state of diabetes mellitus. The perivascular mesenteric fat pad of the non-diabetic BB rats was intermediate between those of the Wistar control and diabetic BB rats. The wet weight of the mesenteric arteries following removal of fat, vein and connective tissues was significantly greater in diabetic BB rats than in the corresponding controls. Microsomal membranes isolated from the mesenteric arteries of diabetic BB rats showed increased alkaline phosphatase and 5'-nucleotidase activities compared to those isolated from the two groups of non-diabetic control rats. Acid phosphatase activities were higher in both BB rat groups compared to the Wistar group.The total Ca²⁺ uptake by the microsomes of mesenteric arteries in the presence of ATP was not different among three experimental groups, but the ATP-dependent active transport of Ca²⁺ was significantly increased and the passive Ca²⁺ binding was significantly reduced in diabetic group compared to the other two non-diabetic groups. Our results demonstrate that in the spontaneously diabetic BB rats, alterations in both structural and functional parameters may underline the vascular complications associated with type I diabetes mellitus in humans.

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The roles of intracellular Ca²⁺ store and protein kinase C (PKC) in vascular contractile responses independent of Ca²⁺ influx were studied using aortic rings from spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat (WKY). The functional sizes of agonistsensitive intracellular Ca²⁺ store were estimated as the peak response to agonist after PKC inhibition with calphostin C (Cal-C), a PKC inhibitor. The participation of PKC in 5-hydroxytryptamine-, phenylephrine-, and endothelin-1 (ET-1)-induced contractions in aortae of SHR was equal to, or greater than that in WKY. In contrast, compared with WKY, SHR aortae possessed a greater size of endothelin-1-sensitive Ca²⁺ store, a similar size of 5-hydroxytryptamine-sensitive Ca²⁺ store, and a smaller size of phenylephrinesensitive Ca²⁺ store. Based on these data, both PKC activation and functional size of intracellular Ca²⁺ store differ between SHR and WKY and these differences are selective among agosists.

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