Effect of prostaglandin inhibition on the hypertensive action of sodium-retaining steroids.

Abstract

SUMMARY To compare the sodium-retaining action and the effect on blood pressure (BP) of certain steroids, nine nonnotensive subjects were given fludrocortisone 0.3 rag orally twice a day (b.i.d.), five received deoxycorticosterone acetate (DOCA) 10 rag IM b.i.d., and this was compared to the effect of fludrocortisone or DOCA plus prostaglandin inhibition (PI) or PI given alone. PI was accomplished with either indomethacin 50 mg or ibuprofen 400 mg every 6 hours. All patients received 250 mEq Na + daily. Fludrocortisone alone caused a cumulative Na + balance of 305 ± 46 (SE) mEq and a weight gain of 2.5 ± 0.1 kg with escape by Day 7. Mean blood pressure (MAP) increased 9 ± 2 mm Hg in both supine and standing positions by Day 8. When fludrocortisone was continued for 16 days, BP rose 14 ± 1 and 11 ± 1 mm Hg respectively. DOCA caused similar Na + retention of 485 ± 125 mEq, weight gain of 2 kg, and escape by Day 7; however, no change in BP was observed. PI alone caused retention of 125 ± 49 mEq, weight gain of 1 kg, and escape by Day 4, but no change in BP. In contrast, fludrocortisone with PI added on Day 9 increased BP 21 ± 2 supine (p < 0.01) and 19 ± 2 mm Hg standing (p < 0.001) compared with fludrocortisone alone, but no greater change in Na + or weight was observed. DOCA plus PI also resulted in no greater Na + retention or change in weight than DOCA alone; however, BP increased from 86 ± 3 to 98 ± 2 mm Hg (p < 0.01). Similar suppression in PRA and aldosterone was noted in all of the study groups. We conclude that: 1) fludrocorticone has a pressor action in normal humans Independent of its effect on sodium balance; 2) DOCA, a pure mineralocorticoid, does not alter BP when given for a period of weeks; 3) PI in normal humans causes some retention of sodium, but does not alter BP; 4) prostaglandin synthesis inhibitors potentiate the pressor action of fludrocortisone and raise BP in DOCA-treated humans, suggesting that vascular prostaglandins play a modulating role in BP control. In the dog, metapyrone increases DOC secretion and elevates the BP by increasing the peripheral resistance, which is not affected by adrenergic blockade. 8' * Prostaglandins of the E and I series are potent vasodilators that can be synthesized by vascular and renal tissues. They may be modulators active in BP homeostasis. Inhibition of prostaglandin synthesis is associated with both sodium retention and an increase in BP in the dog and rabbit.

ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly

“…218 -221 NSAIDs may also contribute to increased vascular resistance due to increased ET-1 synthesis and/or altered arachidonic metabolism. [222][223][224][225][226] They also interfere with BP control in the elderly through partial reversal of antihypertensive effects of diuretics, 218,[227][228][229][230] beta-receptor antagonists, and ACEIs [231][232][233] and ARBs, but not CAs. NSAIDs antagonize antihypertensive effects of beta blockers more than vasodilators or diuretics.…”

ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly

“…NSAIDs may also contribute to increased vascular resistance due to increased ET-1 synthesis and/or altered arachidonic metabolism (222)(223)(224)(225)(226). They also interfere with BP control in the elderly through partial reversal of antihypertensive effects of diuretics (218,(227)(228)(229)(230), beta-receptor antagonists, and ACEIs (231-233) and ARBs, but not CAs.…”

Low-dose Iloprost infusion improves insulin action and non-oxidative glucose metabolism in hypertensive patients

“…As far as PGI2 and blood pressure control is concerned, it has been demonstrated that PGI2 modulates vascular reactivity and blood pressure by different pathophysiological mechanisms [5]. PGI2 systhesis occurs in capillary endothelium and its inhibition by indomethacin administration enhances vascular responsiveness to vasoconstrictors, raising arterial blood pressure [18][19][20]. Furthermore, rats predisposed to salt-induced hypertension exhibit impaired generation of vascular PGIz compared with appropriate control animals [21].…”