| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | British Journal of Pharmacology | ||||
| Publisher: | NATURE PUBLISHING GROUP | ||||
| Place of Publication: | LONDON | ||||
| Volume: | 136 | ||||
| Number of Issue or Book Chapter: | 8 | ||||
| Page Range: | pp. 1117-1126 | ||||
| Date: | 2002 | ||||
| Institutions: | Medicine > Lehrstuhl für Innere Medizin II Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) | ||||
| Identification Number: |
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| Keywords: | SPONTANEOUSLY HYPERTENSIVE RAT; NITRIC-OXIDE SYNTHASE; RENIN GENE-EXPRESSION; CYCLOOXYGENASE-2 EXPRESSION; ANTIINFLAMMATORY DRUGS; SODIUM INTAKE; NACL INTAKE; IN-VITRO; PROSTAGLANDIN; PROSTACYCLIN; hypertension; cyclo-oxygenase-2; aldosterone; renin; SHR; prostaglandin; blood pressure; kidney | ||||
| Dewey Decimal Classification: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 72820 |
Web of ScienceAbstract
1 It is known that nonselective cyclo-oxygenase (COX) inhibitors have small but significant effects on blood pressure (BP), most notably in hypertensive patients on antihypertensive medication. Whether selective COX-2 inhibitors also interfere with BP regulation is not well understood. Therefore, we aimed to examine the effect of chronic treatment with a selective COX-2 inhibitor (rofecoxib) on ...
Abstract
1 It is known that nonselective cyclo-oxygenase (COX) inhibitors have small but significant effects on blood pressure (BP), most notably in hypertensive patients on antihypertensive medication. Whether selective COX-2 inhibitors also interfere with BP regulation is not well understood. Therefore, we aimed to examine the effect of chronic treatment with a selective COX-2 inhibitor (rofecoxib) on systolic blood pressure (sBP) in normotensive Wistar-Kyoto rats (WKY) and on the developmental changes of sBP in young spontaneously hypertensive rats (SHR). In addition, we investigated a possible influence of salt intake on the effects of COX-2 inhibition on BP in these two rat strains. 2 Rofecoxib dose dependently increased sBP and decreased plasma levels of 6-keto prostaglandin (PG)F-1alpha in WKY rats fed a normal salt diet (0.6% NaCl, wt wt(-1)), without affecting serum thromboxane (TX)B-2 levels. 3 Rofecoxib significantly elevated sBP in both rat strains fed normal salt or high salt diet (8% NaCl, wt wt-1), but not in rats on low salt intake (0.02% NaCl, wt wt(-1)). 4 Rofecoxib significantly decreased plasma levels of 6-keto PGF(1alpha), in both rat strains fed normal or high salt diet, but not in rats during low salt intake. 5 Rofecoxib exerted no influence on the changes of body weight nor on water intake. Plasma renin activity (PRA) and renocortical renin mRNA abundance were not changed by rofecoxib, but plasma aldosterone concentration (PAC) was significantly reduced. 6 These results suggest that chronic inhibition of COX-2 causes an increase of blood pressure that depends on prostacyclin synthesis. Furthermore, this increase is independent on genetic predisposition and can be prevented by salt deprivation. Since water intake and body weight gain were not changed by rofecoxib, fluid retention appears not to be a major reason for the development of hypertension. Similarly, an activation of the renin-angiotensin-aldosterone axis appears to be an unlikely candidate mechanism.
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