Hypertension increases the participation of vasoconstrictor prostanoids from cyclooxygenase-2 in phenylephrine responses.

Abstract

OBJECTIVE:

The present study was designed to analyse whether hypertension alters the involvement of cyclooxygenase-2-derived mediators in phenylephrine-induced vasoconstrictor responses.

METHODS:

Vascular reactivity experiments were performed in aortic segments from normotensive, Wistar-Kyoto, and spontaneously hypertensive rats (SHR); protein expression was measured by western blot and/or immunohistochemistry, and prostaglandin F2alpha (PGF2alpha), 8-isoprostane and prostacyclin release were determined by enzyme immunoassay commercial kits.

RESULTS:

The protein synthesis inhibitor dexamethasone (1 micromol/l), the non-selective cyclooxygenase inhibitor indomethacin (10 micromol/l), the selective cyclooxygenase-2 inhibitor NS 398 (1 micromol/l), and the thromboxane A2/prostaglandin H2 (TP) receptor antagonist SQ 29,548 (1 micromol/l), reduced the concentration-response curves to phenylephrine more in segments from hypertensive than from normotensive rats; however, the thromboxane A2 (TxA2) synthase inhibitors furegrelate (10 micromol/l) and OKY 046 (1 and 10 micromol/l) had no effect in either strain. Removing endothelium or adding dexamethasone almost abolished the NS 398 effect. Cyclooxygenase-2 protein expression, which was reduced by dexamethasone, was higher in aorta from hypertensive animals. In both strains cyclooxygenase-2 was localized mainly in endothelial cells and adventitial fibroblasts. 13,14-Dihydro-15-keto-PGF2alpha, 6-keto-PGF1alpha and 8-isoprostane levels were greater in the medium from hypertensive than from normotensive rats; NS 398 decreased levels of the three metabolites studied only in the medium from SHR.

CONCLUSIONS:

PGF2alpha and 8-isoprostane seem to be involved in the response to phenylephrine in rat aorta; this involvement is greater in hypertensive rats, probably due to a higher endothelial induction of cyclooxygenase-2.

• Authors: Yolanda Alvarez, Ana M Briones, Gloria Balfagón, María J Alonso, Mercedes Salaices
• Journal: Journal of hypertension (J Hypertens) Vol. 23 Issue 4 Pg. 767-77 (Apr 2005) ISSN: 0263-6352 [Print] England
• PMID: 15775781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Nitrobenzenes
• Prostaglandins
• Sulfonamides
• Vasoconstrictor Agents
• N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
• Phenylephrine
• 15-keto-13,14-dihydroprostaglandin F2alpha
• 8-epi-prostaglandin F2alpha
• Dinoprost
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases

Topics

• Animals
• Aorta (physiology)
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• Dinoprost (analogs & derivatives, metabolism)
• Endothelium, Vascular (enzymology)
• Hypertension (metabolism)
• Male
• Nitrobenzenes (pharmacology)
• Phenylephrine (pharmacology)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Prostaglandins (metabolism)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Sulfonamides (pharmacology)
• Vasoconstriction (drug effects, physiology)
• Vasoconstrictor Agents (pharmacology)