ATP-sensitive potassium channels do not mediate vasorelaxation by acetylcholine or iloprost

The influence of glibenclamide(GBC), a blocker of ATP-sensitive K+ channells, on relaxation caused by cromakalin(CKL), acetylcholine (ACh) and iloprost (ILO) was assessed in aortic rings (AR) with (E+) or without endotheliium (E-) and in the perfused arterial mesentery (MES) of the rat. In AR preconstricted with noradrenaline, CKL(0.03-10 *M) and ILO (5.5 nM) caused graded vasodilations which were not modified by endothelium removal. ACh(0.01-3 *M) only relaxed E+AR preparations. GBC (3*M) markedly reduced responses to CKL in E+AR and E-AR, but did not affect vasodilation induceds by ILO in E-AR and by ACH in E+AR. In MES preconstricted with methoxamine, bolus injections of CKL (10 or 30 nmol) or ACh (0.03-1nmol) caused graded reductions of perfusion pressure. Only the responses to CKL were significantly inhibited by GBC (10 *M). We conclude that AR and MES contain functional ATP-sensitive K+ channels, which, however, do not play a significant role in the endothelium-dependent vasodilation triggered by ACh or in the endothelium-indipendent relaxation induced by ILO

Availability of calcium for noradrenergic contraction of the mouse isolated vas deferens is not altered during tolerance to and dependence on morphine

1. The present study assesses the influence of tolerance to, and dependence on morphine on the availability of Ca2+ for contraction of the mouse isolated vas deferens induced by noradrenaline (NA). 2. Reducing Ca2+ content in the bathing solution from 2.5 to 1.2 or 0.6 mM significantly reduced the magnitude of NA-induced contractions. This effect was similar in preparations obtained form control and tolerant/dependent mice (P > 0.05 at any Ca2+ concentration). 3. Omission of Ca2+ from the bathing solution caused a rapid and similar loss of responsiveness to a macimally effective concentration of NA (300 micronM) in both groups (t1/2 < 3 min, P > 0.05). 4. Vasa deferentia obtained from control and tolerant/dependent mice were equally sysceptible to non-competitive antagonism of NA-induced contraction by verapamil (3 to 30 micronM; pD2' values of 5.50 and 5.26, rspectively, (P > 0.05 at any concentration of verapamil). 5. Preparations from tolerant/dependent mice displalyed significant supersensitivity to NA, the magnitude of which was not influence by modifying the Ca2+ concentration in the bathing medium (2.6-and 1.7-fold in 0.6 and 2.5mMCa2+, respectively, P < 0.05. 6. I conclude that tolerance to and dependence on morphine are not associated with changes in the availability of Ca2+ for NA-induced contractions of the mouse vas deferens

Microinjection of D-2-amino-7-phosphonoheptanoate into the dorsal periaqueductal gray matter reduces the pressor response to, glutamate injected at the same site

The current study assesses the influence of the N-methil-D-aspartate (NMDA) receptor antagonist D-2-amino-7-phosphonohepatanoate (AP7) on the pressor effect of glutamate microinjected into the dorsal periaqueductal gray matter (DPAG) of urethane-anesthetized rats. Glutamate (20, 40 and 80 nmol/site) caused dose-related reproducible increases in systolic and diastolic blood pressure. Microinjection of saline into the DPAG did not alter the pressor effects of glutamate (80 nmol/site). Similar pretreatment with AP7 (2nmol/site) significantly (P < 0.05) attenuated the pressor effects of glutamate from ñ26.5 ñ 7.0 to +3.4 ñ 3.3 mmHg (sistolic blood pressure). We conclude that the pressor efffect of glutamate in the DPAG is mediated largely by activation of NMDA receptors