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- Publisher Website: 10.1016/j.ejphar.2020.173275
- Scopus: eid_2-s2.0-85087081418
- PMID: 32535100
- WOS: WOS:000554893000010
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Article: Long-term nitric oxide synthase inhibition prevents 17β-estradiol-induced suppression of cyclooxygenase-dependent contractions and enhancement of endothelium-dependent hyperpolarization-like relaxation in mesenteric arteries of ovariectomized rats
Title | Long-term nitric oxide synthase inhibition prevents 17β-estradiol-induced suppression of cyclooxygenase-dependent contractions and enhancement of endothelium-dependent hyperpolarization-like relaxation in mesenteric arteries of ovariectomized rats |
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Authors | |
Keywords | 17β-estradiol Cyclooxygenase Endothelium-derived hyperpolarization Nitric oxide synthase inhibition Ovariectomy |
Issue Date | 2020 |
Publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejphar |
Citation | European Journal of Pharmacology, 2020, v. 882, p. article no. 173275 How to Cite? |
Abstract | Endothelial dysfunction is associated with a reduced bioavailability of nitric oxide (NO). In this study, the effects of 17β-estradiol supplement on endothelial function were examined in ovariectomized (OVX) rats following long-term inhibition of NO synthases with L-NAME. Female Sprague Dawley rats were ovariectomized at 12 weeks old. They were supplemented with 17β-estradiol (25 μg/kg/day, intramuscularly) or its vehicle (olive oil) until they were killed. At 18 weeks old, they were administered daily with NO synthase inhibitor L-NAME (60 mg/kg, by gavage) or its vehicle (distilled water) for 6 weeks. Rats were then anesthetized for blood pressure measurement and for isolation of mesenteric arteries and aortae for isometric tension measurement. Long-term L-NAME-treatment, without or with 17β-estradiol supplement, resulted in reduced plasma nitrite/nitrate level without causing an increase in blood pressure in OVX rats. Acute inhibition of cyclooxygenase (COX) with indomethacin improved relaxations of mesenteric arteries to the calcium ionophore A23187 in OVX rats, and in those with long-term L-NAME-treatment without or with 17β-estradiol supplement, but not in those with female hormone supplement only. 17β-estradiol supplement or long-term L-NAME-treatment resulted in a greater endothelium-dependent hyperpolarization-like relaxation in mesenteric arteries. In the quiescent aorta, 17β-estradiol supplement or long-term L-NAME-treatment unmasked the COX-dependent components of A23187-induced contractions, but prevented that of the smooth muscle contractions to U46619 in OVX rats. In summary, long-term 17β-estradiol-supplement results in differential effects in different blood vessel types, and its beneficial vascular effects are masked under the conditions with NO synthase inhibition. |
Persistent Identifier | http://hdl.handle.net/10722/290637 |
ISSN | 2023 Impact Factor: 4.2 2023 SCImago Journal Rankings: 1.055 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Shi, Y | - |
dc.contributor.author | Leung, SWS | - |
dc.date.accessioned | 2020-11-02T05:45:01Z | - |
dc.date.available | 2020-11-02T05:45:01Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | European Journal of Pharmacology, 2020, v. 882, p. article no. 173275 | - |
dc.identifier.issn | 0014-2999 | - |
dc.identifier.uri | http://hdl.handle.net/10722/290637 | - |
dc.description.abstract | Endothelial dysfunction is associated with a reduced bioavailability of nitric oxide (NO). In this study, the effects of 17β-estradiol supplement on endothelial function were examined in ovariectomized (OVX) rats following long-term inhibition of NO synthases with L-NAME. Female Sprague Dawley rats were ovariectomized at 12 weeks old. They were supplemented with 17β-estradiol (25 μg/kg/day, intramuscularly) or its vehicle (olive oil) until they were killed. At 18 weeks old, they were administered daily with NO synthase inhibitor L-NAME (60 mg/kg, by gavage) or its vehicle (distilled water) for 6 weeks. Rats were then anesthetized for blood pressure measurement and for isolation of mesenteric arteries and aortae for isometric tension measurement. Long-term L-NAME-treatment, without or with 17β-estradiol supplement, resulted in reduced plasma nitrite/nitrate level without causing an increase in blood pressure in OVX rats. Acute inhibition of cyclooxygenase (COX) with indomethacin improved relaxations of mesenteric arteries to the calcium ionophore A23187 in OVX rats, and in those with long-term L-NAME-treatment without or with 17β-estradiol supplement, but not in those with female hormone supplement only. 17β-estradiol supplement or long-term L-NAME-treatment resulted in a greater endothelium-dependent hyperpolarization-like relaxation in mesenteric arteries. In the quiescent aorta, 17β-estradiol supplement or long-term L-NAME-treatment unmasked the COX-dependent components of A23187-induced contractions, but prevented that of the smooth muscle contractions to U46619 in OVX rats. In summary, long-term 17β-estradiol-supplement results in differential effects in different blood vessel types, and its beneficial vascular effects are masked under the conditions with NO synthase inhibition. | - |
dc.language | eng | - |
dc.publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejphar | - |
dc.relation.ispartof | European Journal of Pharmacology | - |
dc.subject | 17β-estradiol | - |
dc.subject | Cyclooxygenase | - |
dc.subject | Endothelium-derived hyperpolarization | - |
dc.subject | Nitric oxide synthase inhibition | - |
dc.subject | Ovariectomy | - |
dc.title | Long-term nitric oxide synthase inhibition prevents 17β-estradiol-induced suppression of cyclooxygenase-dependent contractions and enhancement of endothelium-dependent hyperpolarization-like relaxation in mesenteric arteries of ovariectomized rats | - |
dc.type | Article | - |
dc.identifier.email | Leung, SWS: swsleung@hku.hk | - |
dc.identifier.authority | Leung, SWS=rp00235 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.ejphar.2020.173275 | - |
dc.identifier.pmid | 32535100 | - |
dc.identifier.scopus | eid_2-s2.0-85087081418 | - |
dc.identifier.hkuros | 317948 | - |
dc.identifier.volume | 882 | - |
dc.identifier.spage | article no. 173275 | - |
dc.identifier.epage | article no. 173275 | - |
dc.identifier.isi | WOS:000554893000010 | - |
dc.publisher.place | Netherlands | - |
dc.identifier.issnl | 0014-2999 | - |