Effect of rofecoxib on antihypertensive effects of candesartan in experimental models of hypertension.
Given the high prevalence of hypertension, concomitant use of nonsteroidal anti-inflammatory drugs and antihypertensive medications is commonly encountered in clinical practice. The present study was designed to study the effect of indomethacin, nimesulide, and rofecoxib on blood pressure (BP) in normotensive and hypertensive rats and also to investigate the effect of rofecoxib on BP control in candesartan-treated hypertensive rats. Male Wistar rats weighing 150-200 g were divided into three groups: control, DOCA-hypertensive, and L-NAME-hypertensive rats. All the rats were given indomethacin (15 mg/kg body weight), nimesulide (20 mg/kg body weight), rofecoxib (10 mg/kg body weight), or vehicle orally and daily for 6 weeks. Hypertensive rats in separate groups were treated with either candesartan (1 mg/kg body weight) alone or a combination of candesartan (1 mg/kg body weight) and rofecoxib (10 mg/kg body weight) orally and daily for 6 weeks. BP measurements were performed using tail cuff method at baseline and 1-week intervals throughout the treatment period. All the three COX inhibitors resulted in increase in BP, but mean change in BP was the highest with rofecoxib. Rofecoxib-treated L-NAME-hypertensive rats exhibited a significant increase in mean arterial pressure at 6 weeks (168.3+/-5.7 mmHg) as compared with DOCA-hypertensive rats (128.818+/-7.2 mmHg). Administration of Rofecoxib L-NAME-hypertensive rats treated with candesartan resulted in a significant increase in BP. Systolic BP at 0 week (107.0+/-4.2 mmHg) rose to 141.6+/-2.0 mmHg at 6 weeks. Systolic BP at 2, 4, and 6 weeks was significantly higher as compared with (L-NAME+candesartan)- and (rofecoxib+candesartan)-treated group. In conclusion, concomitant use of rofecoxib resulted in poor BP control by candesartan in L-NAME-hypertensive rats.
Jain
S
S
Department of Pharmacology, PGIMER, Chandigarh, India.
Gupta
M
M
Malhotra
S
S
Pandhi
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D007783:Lactones / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013450:Sulfones / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D013777:Tetrazoles / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007783:Lactones; D013450:Sulfones; D013777:Tetrazoles; C116926:rofecoxib; C081643:candesartan