Hypertension indomethacin effect

In two kidney-one clip hypertensive rabbits without significant impairment of renal function, treatment with indomethacin for 10 days is without effect on blood pressure although it reduces plasma renin activity . In contrast, in two kidney-one clip hypertensive rabbits having high plasma renin activity and depressed renal haemodynamics, chronic treatment with indomethacin aggravates both the hypertension and the renal function impairment . In the latter study, plasma renin activity, which initially was reduced by indomethacin, returned on subsequent days to pretreatment levels pari passu with the increase in blood pressure and the deterioration of renal function . Chronic indomethacin treatment also exacerbates the hypertension, and depresses renal excretory function, in rats with two kidney-one clip hypertension . However, short-term treatment with indomethacin lowers blood pressure, associated with reduction of plasma renin activity, in rats with two clip—one kidney hypertension . Indomethacin also produces correlated decrements of blood pressure and plasma renin activity in rats made hypertensive by complete ligation of the aorta between the renal arteries . In contrast, shortterm treatment with indomethacin or meclofenamate is without effect on blood pressure in dogs with two kidney—one clip hypertension . 

In patients with essential hypertension, indomethacin, given by in intramuscular injection at 1 mgkg increases blood pressure and total peripheral vascular resistance associated with diminution of cardiac output". However, reports that indomethacin, given orally at 75-200 mg day for 4-7 days, increases blood pressure in patients with untreated, uncomplicated, essential hypertension contrasts with reports that it does not . Cyclo-oxygenase inhibitors, indomethacin and ibuprofen, were also without effect on blood pressure in patients with renovascular hypertension . Yet, in two siblings with renin-dependent hypertension and aldosteronism, the administration of indomethacin at 250 mg day for 16 days was found to lower blood pressure and plasma renin activity, despite promoting slight retention of salt and water ... 

Indomethacin was used traditionally, but its relative cyclooxygenase-1 (COX-1) selectivity theoretically increases its gastropathy risk. Thus other generic NSAIDs may be preferred. Adverse effects of NSAIDs include gastropathy (primarily peptic ulcers), renal dysfunction, and fluid retention. NSAIDs generally should be avoided in patients at risk for peptic ulcers, those taking warfarin, and those with renal insufficiency or uncontrolled hypertension or heart failure. 

Selectivity for COX-1 versus COX-2 is variable and incomplete for the older NSAIDs, but many selective COX-2 inhibitors have been synthesized. The selective COX-2 inhibitors do not affect platelet function at their usual doses. In testing using human whole blood, aspirin, ibuprofen, indomethacin, piroxicam, and sulindac are somewhat more effective in inhibiting COX-1. The efficacy of -2-selective drugs equals that of the older NSAIDs, while gastrointestinal safety may be improved. On the other hand, selective COX-2 inhibitors may increase the incidence of edema and hypertension. As of December 2008, celecoxib and the less selective meloxicam are the only COX-2 inhibitors marketed in the USA. Rofecoxib and valdecoxib, two previously marketed, selective COX-2 inhibitors, have been withdrawn from the market due to their association with increased cardiovascular thrombotic events. Celecoxib has an FDA-initiated "black box" warning concerning cardiovascular risks. It has been recommended that all NSAID product labels be revised to include cardiovascular risks. 

Chalmers JP, West MJ, Wing LM, Bune AJ, Graham JR. Effects of indomethacin, sulindac, naproxen, aspirin, and paracetamol in treated hypertensive patients. Clin Exp Hypertens A 1984 6(6) 1077-93. 

Fogari R, Zoppi A, Carretta R et al. Effect of indomethacin on the antihypertensive efficacy of valsartan and lisinopriha multicentre study. Journal of Hypertension 2002 20 1007-1014. 

Conlin PR, Moore TJ, Swartz SL, Barr E, Gazdick L, Fletcher C, DeLucca P, Demopoulos L. Effect of indomethacin on blood pressure lowering by captopril and losailan in hypertensive patients. Hypertension (2000) 36,461-5. 

Lopez-Ovejero JA, Weber MA, Drayer JIM, Sealey JE, Laragh JH. Effects of indomethacin alone and during diuretic or beta-a(henoceptor blockade therapy on blood pressure and the renin system in essential hypertension. Clin Sci Mol Med (1978) 55,203S-205S. 

That therapy with various types of antihypertensive agents causes prostanoid levels to increase, raises the possibility that the accompanying blood pressure lowering effect is related to the increase in prostanoids. Pertaining to this point, several studies have demonstrated that indomethacin treatment at 75-200 mg day consistently raises blood pressure, sometimes by as much as 30mmHg, in hypertensive patients undergoing therapy with... 

Stahl, R., Dienemann, H., Besserer, K., Kneissler, U. and Helmchen, U. (1981). Effect of indomethacin on blood pressure in rats with renovascular hypertension Dependence on plasma renin activity. Klin. Wochenschr., 59, 245-246... 

Romero, J.C. and Strong, C.G. (1977). The effect of indomethacin blockade of prostaglandin synthesis on blood pressure of normal rabbits and rabbits with renovascular hypertension. Circ. Res., 40, 35-40... 

Dietz, J.R., Davis, J.O., DeForrest, J.M., Freeman, R.H., Echtenkamp, S.F. and Seymour, A.A. (1981). Effects of indomethacin in dogs with acute and chronic renovascular hypertension. Am. ]. Physiol, 240, H533-H538... 

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