Korean J Physiol Pharmacol.  2017 Jul;21(4):407-413. 10.4196/kjpp.2017.21.4.407.

Participation of COX-1 and COX-2 in the contractile effect of phenylephrine in prepubescent and old rats

Affiliations
  • 1Cardiovascular Pharmacology and Hyperbaric Experimental Medicine, Escuela Superior de Medicina, Instituto Politecnico Nacional, 11340 Mexico City, Mexico. castillohernandezmc@gmail.com, ccastillohe@yahoo.com.mx

Abstract

Vascular reactivity can be influenced by the vascular region, animal age, and pathologies present. Prostaglandins (produced by COX-1 and COX-2) play an important role in the contractile response to phenylephrine in the abdominal aorta of young rats. Although these COXs are found in many tissues, their distribution and role in vascular reactivity are not clear. At a vascular level, they take part in the homeostasis functions involved in many physiological and pathologic processes (e.g., arterial pressure and inflammatory processes). The aim of this study was to analyze changes in the contractile response to phenylephrine of thoracic/abdominal aorta and the coronary artery during aging in rats. Three groups of rats were formed and sacrificed at three distinct ages: prepubescent, young and old adult. The results suggest that there is a higher participation of prostanoids in the contractile effect of phenylephrine in pre-pubescent rats, and a lower participation of the same in old rats. Contrarily, there seems to be a higher participation of prostanoids in the contractile response of the coronary artery of older than pre-pubescent rats. Considering that the changes in the expression of COX-2 were similar for the three age groups and the two tissues tested, and that expression of COX-1 is apparently greater in older rats, COX-1 and COX-2 may lose functionality in relation to their corresponding receptors during aging in rats.

Keyword

Aorta; Cyclooxygenase; Development; Heart; Phenylephrine

MeSH Terms

Adult
Aging
Animals
Aorta
Aorta, Abdominal
Arterial Pressure
Coronary Vessels
Heart
Homeostasis
Humans
Pathologic Processes
Pathology
Phenylephrine*
Prostaglandin-Endoperoxide Synthases
Prostaglandins
Rats*
Phenylephrine
Prostaglandin-Endoperoxide Synthases
Prostaglandins

Figure

  • Fig. 1 Contractile effects of phenylephrine in thoracic and abdominal aorta.Contractile effect of phenylephrine (1×10−9 to 1×10−5 M) in thoracic aorta (A) and abdominal (B) from pre-pubescent, young and old. Each point represent the mean±S.E.M. n=5. *p≤0.05.

  • Fig. 2 Contractile effect of phenylephrine with indomethacin.Contractile effect of phenylephrine (1×10−9 to 1×10−5 M) in thoracic aorta from 6 weeks old (A), 16 weeks old (B) and 1 year old (C), with and without indomethacin (1×10−5 M). Each point represent the mean±S.E.M. n=5. *p≤0.05.

  • Fig. 3 Effects of indomethacin on the phenylephrine-induced contraction in abdominal aorta.Contractile effect of phenylephrine (1×10−9 to 1×10−5 M) in abdominal aorta from 6 weeks old (A), 16 weeks old (B) and 1 year old (C), with and without indomethacin (1×10−5 M). Each point represent the mean±S.E.M. n=5. *p≤0.05.

  • Fig. 4 Contractile effect of phenylephrine in isolated heart.Contractile effect of phenylephrine (1×10−9 to 1×10−5 M) in isolated heart from 6 weeks old (A), 16 weeks old (B) and 1 year old (C), with and without indomethacin (1×10−5 M). Each point represent the mean±S.E.M. n=5. *p≤0.05.

  • Fig. 5 Effect of SC560 on the phenylephrine-induced contraction.Contractile effect of phenylephrine (1×10−9 to 1×10−5 M) in thoracic and abdominal aorta from 6 weeks old (A) and 1 year old (B), with and without SC560 (1×10−6 M). Each point represent the mean±S.E.M. n=5. *p≤0.05.

  • Fig. 6 Effect of NS398 on the phenylephrine-induced contraction.Contractile effect of phenylephrine (1×10−9 to 1×10−5 M) in thoracic and abdominal aorta from 6 weeks old (A) and 1 year old (B), with and without NS398 (1×10−6 M). Each point represent the mean±S.E.M. n=5. *p≤0.05.

  • Fig. 7 Expression of COX-1 in the aorta and the heart.Expression of COX 1, in thoracic and abdominal aorta and heart from 6 weeks old, 16 weeks old and 1 year old. Each barr represent the mean±S.E.M. n=5. *p≤0.05.

  • Fig. 8 Expression of COX-2 in the aorta and the heart.Expression of COX 2, in thoracic and abdominal aorta and heart from 6 weeks old, 16 weeks old and 1 year old. Each barr represent the mean±S.E.M. n=5. *p≤0.05.


Cited by  1 articles

The physiological and pharmacological roles of prostaglandins in hair growth
Dong Wook Shin
Korean J Physiol Pharmacol. 2022;26(6):405-413.    doi: 10.4196/kjpp.2022.26.6.405.


Reference

1. Castillo-Hernandez MC, Guevara-Balcazar G, Lopez-Sanchez P, Asbun-Bojalil J, Lopez RM, Castillo EF, Castillo-Henkel C. The influence of constitutive COX-2 in smooth muscle tissue on the contractile effect of phenylephrine in the rat abdominal aorta. Front Biosci (Elite Ed). 2010; 2:441–448. PMID: 20036891.
2. Kähönen M, Tolvanen JP, Sallinen K, Wu X, Pörsti I. Influence of gender on control of arterial tone in experimental hypertension. Am J Physiol. 1998; 275:H15–H22. PMID: 9688891.
3. Pairet M, Engelhardt G. Distinct isoforms (COX-1 and COX-2) of cyclooxygenase: possible physiological and therapeutic implications. Fundam Clin Pharmacol. 1996; 10:1–17. PMID: 8900495.
Article
4. Smith WL, Dewitt DL. Prostaglandin endoperoxide H synthases-1 and -2. Adv Immunol. 1996; 62:167–215. PMID: 8781269.
Article
5. Zidar N, Dolenc-Strazar Z, Jeruc J, Jerse M, Balazic J, Gartner U, Jermol U, Zupanc T, Stajer D. Expression of cyclooxygenase-1 and cyclooxygenase-2 in the normal human heart and in myocardial infarction. Cardiovasc Pathol. 2007; 16:300–304. PMID: 17868881.
Article
6. Feng L, Sun W, Xia Y, Tang WW, Chanmugam P, Soyoola E, Wilson CB, Hwang D. Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression. Arch Biochem Biophys. 1993; 307:361–368. PMID: 8274023.
Article
7. O'Neill GP, Ford-Hutchinson AW. Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett. 1993; 330:156–160. PMID: 8365485.
8. Iseki S. Immunocytochemical localization of cyclooxygenase-1 and cyclooxygenase-2 in the rat stomach. Histochem J. 1995; 27:323–328. PMID: 7635765.
Article
9. Luksha L, Poston L, Gustafsson JA, Aghajanova L, Kublickiene K. Gender-specific alteration of adrenergic responses in small femoral arteries from estrogen receptor-beta knockout mice. Hypertension. 2005; 46:1163–1168. PMID: 16216990.
10. Connolly C, McCormick PA, Docherty JR. Effects of the selective cyclooxygenase-2 inhibitor nimesulide on vascular contractions in endothelium-denuded rat aorta. Eur J Pharmacol. 1998; 352:53–58. PMID: 9718267.
Article
11. Gregg AR, Thompson LP, Herrig JE, Weiner CP. Regionalization of endothelium-dependent relaxation in the thoracic aorta of pregnant and nonpregnant guinea pigs. J Vasc Res. 1995; 32:106–111. PMID: 7734656.
Article
12. Perrone MG, Scilimati A, Simone L, Vitale P. Selective COX-1 inhibition: A therapeutic target to be reconsidered. Curr Med Chem. 2010; 17:3769–3805. PMID: 20858219.
13. Matz RL, Van Overloop B, Gaubert E, Gairard A. Maturation reveals a decrease in endothelium-dependent contraction induced by depolarization in the aorta of spontaneously hypertensive rats. Life Sci. 2001; 69:1791–1804. PMID: 11665841.
Article
14. Asbún-Bojalil J, Castillo EF, Escalante BA, Castillo C. Does segmental difference in alpha 1-adrenoceptor subtype explain contractile difference in rat abdominal and thoracic aortae? Vascul Pharmacol. 2002; 38:169–175. PMID: 12402516.
15. Lamb VL, Schwartz AJ, Rohn WR, Kaiser L. Cyclooxygenase inhibitors depress norepinephrine constriction of rat abdominal, but not thoracic, aorta. Eur J Pharmacol. 1994; 256:221–226. PMID: 7914169.
Article
16. Asano K, Lilly CM, Drazen JM. Prostaglandin G/H synthase-2 is the constitutive and dominant isoform in cultured human lung epithelial cells. Am J Physiol. 1996; 271:L126–L131. PMID: 8760142.
Article
17. Hennan JK, Huang J, Barrett TD, Driscoll EM, Willens DE, Park AM, Crofford LJ, Lucchesi BR. Effects of selective cyclooxygenase-2 inhibition on vascular responses and thrombosis in canine coronary arteries. Circulation. 2001; 104:820–825. PMID: 11502709.
Article
18. Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol. 1998; 38:97–120. PMID: 9597150.
Article
19. Morita I. Distinct functions of COX-1 and COX-2. Prostaglandins Other Lipid Mediat. 2002; 68-69:165–175. PMID: 12432916.
Article
20. LaBelle EF, Polyak E. Norepinephrine stimulates arachidonic acid release from vascular smooth muscle via activation of cPLA2. Am J Physiol. 1998; 274:C1129–C1137. PMID: 9575810.
21. Qi Z, Cai H, Morrow JD, Breyer MD. Differentiation of cyclooxygenase 1- and 2-derived prostanoids in mouse kidney and aorta. Hypertension. 2006; 48:323–328. PMID: 16801485.
Article
22. Kangussu LM, Olivon VC, Arifa RD, Araújo N, Reis D, Assis MT, Soriani FM, de Souza Dda G, Bendhack LM, Bonaventura D. Enhancement on reactive oxygen species and COX-1 mRNA levels modulate the vascular relaxation induced by sodium nitroprusside in denuded mice aorta. Fundam Clin Pharmacol. 2015; 29:150–163. PMID: 25619310.
Article
23. Kumar P, Padi SS, Naidu PS, Kumar A. Cyclooxygenase inhibition attenuates 3-nitropropionic acid-induced neurotoxicity in rats: possible antioxidant mechanisms. Fundam Clin Pharmacol. 2007; 21:297–306. PMID: 17521299.
Article
Full Text Links
  • KJPP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr