These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Nitric oxide regulation of TP receptor-mediated pulmonary vasoconstriction in the anesthetized, open-chest rat.
    Author: Valentin JP, Bessac AM, Maffre M, John GW.
    Journal: Eur J Pharmacol; 1996 Dec 19; 317(2-3):335-42. PubMed ID: 8997619.
    Abstract:
    We investigated the influence of endothelial nitric oxide (NO) on the pulmonary pressor activity of the stable thromboxane A2 analogue, U-46619 (9,11-dideoxy-9 alpha-(methanoepoxy) prostaglandin F2 alpha), in anesthetized open-chest Sprague-Dawley rats (n = 6-9 per group). NO synthase inhibition, as obtained by N omega-nitro-L-arginine methyl ester (L-NAME; 0.63 mg/kg i.v. + 20 mg/kg/h), induced sustained systemic hypertension (mean maximal increase, delta, in mean systemic arterial pressure = 38 +/- 6 mmHg; P < 0.05 vs. vehicle) associated with slight bradycardia (delta heart rate = -42 +/- 8 beats/min; P < 0.05 vs. vehicle) and delayed- (> 30 min) onset pulmonary hypertension (delta mean pulmonary arterial pressure = 10 +/- 3.4 mmHg; P < 0.05 vs. vehicle). In separate experiments, when mean systemic arterial pressure was maximally increased by L-NAME, the difference between mean pulmonary arterial pressure and mean left atrial pressure was greater in L-NAME-treated rats (41 +/- 16% compared to 10 +/- 1% in the vehicle group; P < 0.05), strongly suggesting that spontaneously released NO modulated pulmonary vascular resistance. L-Arginine at a dose which reduced by approximately 50% the L-NAME-associated systemic hypertension did not alter the late rise in mean pulmonary arterial pressure (delta mean pulmonary arterial pressure = 12 +/- 4 mmHg; P = NS vs. L-NAME alone). U-46619, elicited rapid, dose-dependent, and transient increases in mean pulmonary arterial pressure (delta = 8.8 +/- 2.0 and 21.2 +/- 1.9 mmHg at 1.25 and 20 micrograms/kg i.v. respectively; both P < 0.01 vs. vehicle). U-46619 (1.25 micrograms/kg)-induced increases in mean pulmonary arterial pressure were fully antagonized by the thromboxane A2/prostanoid (TP) receptor antagonist, SQ 29,548 ([1S-[1 alpha,2 alpha(5Z),3 alpha,4 alpha]]-7-[3-[[2-[(phenyl-amino)-carbonyl] hydrazino] methyl]-7-oxabicyclo [2.2.1]hept-2-yl]-5-heptenoic acid) (0.63 mg/kg i.v. + 0.63 mg/kg/h). Injection of U-46619 (1.25 micrograms/kg), 15 min after L-NAME administration, evoked a 24.7 +/- 0.9 mmHg increase in mean pulmonary arterial pressure (P < 0.01 vs. U-46619 in control rats), which was (i) greater than that produced by a 16-fold higher dose of U-46619 alone, (ii) fully antagonized by SQ 29,548, (iii) significantly attenuated during coadministration of L-NAME and L-arginine (10 mg/kg i.v. + 160 mg/kg/h; delta mean pulmonary arterial pressure = 14.6 +/- 4.3 mmHg; P < 0.05 vs. U-46619 following L-NAME alone and P = NS vs. U-46619 in control rats). These results indicate that, under normal circumstances, pulmonary vasomotor tone is regulated by spontaneously released NO. Moreover, pulmonary vascular NO attenuates TP receptor-mediated pressor responses, strongly suggesting that in addition to mediating pulmonary vasoconstriction, TP receptor activation also concomitantly releases NO within the pulmonary vasculature.
    [Abstract] [Full Text] [Related] [New Search]