Relaxation Response In Rings Research Articles

Postnatal changes in mechanisms mediating acetylcholine-induced relaxation in piglet femoral arteries.

We studied the nitric oxide-cGMP pathway in endothelium-dependent relaxation in femoral arterial rings from piglets at different postnatal ages. Responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined in phenylephrine-precontracted rings from newborn (10-22-h) and 7 d (7-10-d)-old piglets. Relaxant responses were investigated in endothelium-denuded rings and endothelium-intact controls, and in endothelium-intact rings incubated with the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine acetate (L-NMMA), indomethacin, or the superoxide anion generator 6-anilinoquinoline-5,8-quinone (LY83583). Arterial rings from both age groups relaxed to a similar degree in response to ACh. Relaxation in rings from newborn piglets was insensitive to NOS inhibition by L-NMMA, whereas in artery rings from 7-d-old piglets, the relaxant response was significantly inhibited by L-NMMA. Incubation with LY83583 gave an inhibition of ACh-induced relaxation very similar to that of L-NMMA. Incubation with indomethacin had no significant effect on ACh-induced relaxation in either age group. Artery rings from both age groups relaxed 100% to SNP; the 7-d-old group was more sensitive than the newborn. NOS inhibition potentiated SNP-induced relaxation in both groups, but the potentiating effect was of greater magnitude in the newborn. Our results indicate a difference in the mechanism(s) underlying ACh-induced relaxation in the femoral artery from newborn and 7-d-old piglets, with an intact relaxant response in rings from the newborn despite NOS inhibition. The SNP results indicate a down-regulated soluble guanylate cyclase in the newborn, possibly related to a difference in basal NO release between the two age groups.

Oxidized low-density lipoproteins facilitate leukocyte adhesion to aortic intima without affecting endothelium-dependent relaxation. Role of P-selectin.

Inflammatory cell deposition in atherosclerotic blood vessels has been thought to relate to loss of endothelium-derived nitric oxide (NO). To examine whether cell deposition correlates temporally with the loss of NO activity, rat aortic rings were incubated with buffer, native LDL (n-LDL), oxidized LDL (ox-LDL), or the endothelium-derived relaxing factor synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) for 2 hours, and vascular contractile response to norepinephrine and relaxant response to acetylcholine, thrombin, and calcium ionophore A23,187 were examined. Thereafter, the rings were exposed to biotin-fluorescein isothiocyanate-labeled fluorescent or unlabeled leukocytes for 30 minutes. Cell adhesion was quantitated by fluorescent microscopy as well as by scanning electron microscopy. Incubation with n-LDL or ox-LDL did not affect either the contractile or the relaxant response of rings. However, leukocyte adhesion increased markedly in all ox-LDL-treated rings but not in those treated with n-LDL. Thus, leukocyte adhesion occurred independent of NO activity. In keeping with this concept, pretreatment of rings with the NO precursor L-arginine failed to influence leukocyte adhesion to rings incubated with ox-LDL. Treatment of rings with L-NAME also resulted in adhesion of a large number of leukocytes. Furthermore, all rings treated with ox-LDL or L-NAME demonstrated marked expression of P-selectin leukocyte adhesion molecules, determined by immunohistochemistry. Pretreatment of rings with the P-selectin blocking antibody PB1.3 markedly decreased deposition of leukocytes in rings exposed to ox-LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasodilatory Effects of Ketamine on Pulmonary Arteries in Rats with Chronic Hypoxic Pulmoanry Hypertension

To study the effects of ketamine on structurally remodeled pulmonary arteries from rats with hypoxic pulmonary hypertension (PH) and the effects of ketamine on endothelium-dependent and -independent relaxation, rats were exposed to hypobaric hypoxia (air at 380 mm Hg for 10 days). We measured the responses to ketamine, acetylcholine, and sodium nitroprusside (SNP) in prostaglandin F2 alpha-precontracted ring segments from a left extrapulmonary artery (EPA, 1.4-1.6 mm in outside diameter [OD] and an intrapulmonary artery (IPA, 0.7-1.1 mm OD) obtained from control and PH rats. The effects of acetylcholine and SNP were decreased in EPA and IPA rings from PH rats compared with control rings. In contrast, ketamine produced a greater relaxation response in rings from PH rats at 3 x 10(-5) -3 x 10(-4) in the EPA and at 10(-4) -10(-3) M in the IPA compared to control rings. A nitric oxide synthase inhibitor, nitro-L-arginine (10(-4) M), inhibited the relaxation in response to acetylcholine in both control and PH rats. Pretreatment with ketamine (10(-4) M) had no effect on the relaxation response to any concentration of acetylcholine or SNP in either control or PH rats. We conclude that nitric-oxide-mediated relaxation, but not ketamine-induced relaxation, was impaired in structurally remodeled hypertensive pulmonary arteries. Ketamine had no effects on nitric oxide-mediated relaxation in either normal or PH rats.

Relative location of alpha- and beta-adrenoceptors to sites of release of sympathetic transmitter in the rabbit facial vein.

We studied alpha- and beta-adrenoceptor-mediated responses of rabbit facial vein rings to adrenergic stimulation to determine the location of the two types of receptors in relation to the sympathetic nerve terminals. Transmural electrical nerve stimulation (TNS) at low frequency elicited large beta-receptor-mediated relaxation responses in rings pretreated with phentolamine (6 x 10(-7)M). These responses were significantly greater than the corresponding alpha-receptor-mediated contractions in rings pretreated with propranolol (10(-6)M). Blockade of neuronal uptake with desmethylimipramine (DMI, 10(-7)M) increased significantly the neurogenic relaxation but had little effect on neurogenic contractility. DMI pretreatment caused a shift to the left (x 5.6) in the relaxant dose-response curve to exogenous l-norepinephrine (NE). The NE contractile dose-response curve was also shifted to the left after DMI pretreatment but by a significantly smaller amount (x 3.1). Neurogenic activation of beta-receptors evoked almost maximal relaxations in facial vein rings (85% at 2 Hz), whereas the maximum neurogenic contraction was approximately half the maximum contraction with exogenous NE (40% at 6 Hz). These results imply that the beta-adrenoceptors in the rabbit facial vein are located in close proximity to sites of adrenergic transmitter release and neuronal reuptake, whereas the alpha-receptors are more distant.