Tags

Type your tag names separated by a space and hit enter

Effects of nitric oxide synthase inhibition with or without cyclooxygenase-2 inhibition on resting haemodynamics and responses to exendin-4.
Br J Pharmacol. 2006 Nov; 149(6):802-9.BJ

Abstract

BACKGROUND AND PURPOSE

Interactions between the NO system and the cyclooxygenase systems may be important in cardiovascular regulation. Here we measured the effects of acute cyclooxygenase-2 inhibition (with parecoxib), alone and in combination with NOS inhibition (with NG-nitro-L-arginine methyl ester (L-NAME)), on resting cardiovascular variables and on responses to the glucagon-like peptide 1 agonist, exendin-4, which causes regionally-selective vasoconstriction and vasodilatation.

EXPERIMENTAL APPROACH

Rats were instrumented with flow probes and intravascular catheters to measure regional haemodynamics in the conscious, freely moving state. L-NAME was administered as a primed infusion 180 min after administration of parecoxib or vehicle, and exendin-4 was given 60 min after the onset of L-NAME infusion.

KEY RESULTS

Parecoxib had no effect on resting cardiovascular variables or on responses to L-NAME. Exendin-4 caused a pressor response accompanied by tachycardia, mesenteric vasoconstriction and hindquarters vasodilatation. Parecoxib did not affect haemodynamic responses to exendin-4, but L-NAME inhibited its hindquarters vasodilator and tachycardic effects. When combined, L-NAME and parecoxib almost abolished the hindquarters vasodilatation while enhancing the pressor response.

CONCLUSIONS AND IMPLICATIONS

Cyclooxygenase-2-derived products do not affect basal haemodynamic status in conscious normotensive rats, or influence the NO system acutely. The inhibitory effects of L-NAME on the hindquarters vasodilator and tachycardic effects of exendin-4 are consistent with a previous study that showed those events to be beta-adrenoceptor mediated. The additional effect of parecoxib on responses to exendin-4 in the presence of L-NAME, is consistent with other evidence for enhanced involvement of vasodilator prostanoids when NO production is reduced.

Authors+Show Affiliations

Centre for Integrated Systems Biology & Medicine, School of Biomedical Sciences, University of Nottingham, Nottinghamshire, UK. sheila.gardiner@nottingha.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17016494

Citation

Gardiner, S M., et al. "Effects of Nitric Oxide Synthase Inhibition With or Without Cyclooxygenase-2 Inhibition On Resting Haemodynamics and Responses to Exendin-4." British Journal of Pharmacology, vol. 149, no. 6, 2006, pp. 802-9.
Gardiner SM, March JE, Kemp PA, et al. Effects of nitric oxide synthase inhibition with or without cyclooxygenase-2 inhibition on resting haemodynamics and responses to exendin-4. Br J Pharmacol. 2006;149(6):802-9.
Gardiner, S. M., March, J. E., Kemp, P. A., & Bennett, T. (2006). Effects of nitric oxide synthase inhibition with or without cyclooxygenase-2 inhibition on resting haemodynamics and responses to exendin-4. British Journal of Pharmacology, 149(6), 802-9.
Gardiner SM, et al. Effects of Nitric Oxide Synthase Inhibition With or Without Cyclooxygenase-2 Inhibition On Resting Haemodynamics and Responses to Exendin-4. Br J Pharmacol. 2006;149(6):802-9. PubMed PMID: 17016494.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of nitric oxide synthase inhibition with or without cyclooxygenase-2 inhibition on resting haemodynamics and responses to exendin-4. AU - Gardiner,S M, AU - March,J E, AU - Kemp,P A, AU - Bennett,T, Y1 - 2006/10/03/ PY - 2006/10/4/pubmed PY - 2007/2/13/medline PY - 2006/10/4/entrez SP - 802 EP - 9 JF - British journal of pharmacology JO - Br J Pharmacol VL - 149 IS - 6 N2 - BACKGROUND AND PURPOSE: Interactions between the NO system and the cyclooxygenase systems may be important in cardiovascular regulation. Here we measured the effects of acute cyclooxygenase-2 inhibition (with parecoxib), alone and in combination with NOS inhibition (with NG-nitro-L-arginine methyl ester (L-NAME)), on resting cardiovascular variables and on responses to the glucagon-like peptide 1 agonist, exendin-4, which causes regionally-selective vasoconstriction and vasodilatation. EXPERIMENTAL APPROACH: Rats were instrumented with flow probes and intravascular catheters to measure regional haemodynamics in the conscious, freely moving state. L-NAME was administered as a primed infusion 180 min after administration of parecoxib or vehicle, and exendin-4 was given 60 min after the onset of L-NAME infusion. KEY RESULTS: Parecoxib had no effect on resting cardiovascular variables or on responses to L-NAME. Exendin-4 caused a pressor response accompanied by tachycardia, mesenteric vasoconstriction and hindquarters vasodilatation. Parecoxib did not affect haemodynamic responses to exendin-4, but L-NAME inhibited its hindquarters vasodilator and tachycardic effects. When combined, L-NAME and parecoxib almost abolished the hindquarters vasodilatation while enhancing the pressor response. CONCLUSIONS AND IMPLICATIONS: Cyclooxygenase-2-derived products do not affect basal haemodynamic status in conscious normotensive rats, or influence the NO system acutely. The inhibitory effects of L-NAME on the hindquarters vasodilator and tachycardic effects of exendin-4 are consistent with a previous study that showed those events to be beta-adrenoceptor mediated. The additional effect of parecoxib on responses to exendin-4 in the presence of L-NAME, is consistent with other evidence for enhanced involvement of vasodilator prostanoids when NO production is reduced. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/17016494/Effects_of_nitric_oxide_synthase_inhibition_with_or_without_cyclooxygenase_2_inhibition_on_resting_haemodynamics_and_responses_to_exendin_4_ L2 - https://doi.org/10.1038/sj.bjp.0706931 DB - PRIME DP - Unbound Medicine ER -