title: Cyclo-oxygenase-2 inhibition increases blood pressure in rats.
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.
authors.affiliation: Institut für Pharmakologie, Universitätsstr. 31, 93040 Regensburg, Germany. klaus.hoecherl@chemie.uni-regensburg.de
authors.forename: Klaus
authors.initials: K
authors.lastname: Höcherl
authors.forename: Dierk
authors.initials: D
authors.lastname: Endemann
authors.forename: Martin C
authors.initials: MC
authors.lastname: Kammerl
authors.forename: Horst F
authors.initials: HF
authors.lastname: Grobecker
authors.forename: Armin
authors.initials: A
authors.lastname: Kurtz
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000199:Actins / Q000378:metabolism; D000450:Aldosterone / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007783:Lactones / Q000009:adverse effects*; D008297:Male; D011188:Potassium / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012083:Renin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D012982:Sodium, Dietary / Q000008:administration & dosage; D013450:Sulfones
chemical_list: D000199:Actins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D012333:RNA, Messenger; D012982:Sodium, Dietary; D013450:Sulfones; C116926:rofecoxib; D000450:Aldosterone; D015121:6-Ketoprostaglandin F1 alpha; D012083:Renin; D011188:Potassium