A patient taking indomethacin develops worsening of pre-existing hypertension and oedema. The mechanism by which NSAIDs cause sodium retention and blood pressure elevation is best described as:

• A Direct activation of aldosterone receptors in the collecting duct
• B Inhibition of renal medullary COX-2, reducing PGE2 and PGI2, which normally oppose ADH-mediated water retention and facilitate natriuresis ✓
• C Increased thromboxane A2 production causing renal arterial vasoconstriction
• D Stimulation of renin secretion via beta-1 adrenoceptors in the juxtaglomerular apparatus

Explanation

In the kidney, prostaglandins PGE2 and PGI2 (synthesised by COX-1 and COX-2 in the medulla) play important roles: they oppose the antidiuretic effect of ADH on the collecting duct, promote natriuresis in the thick ascending limb, and maintain GFR via afferent arteriole vasodilation (especially when renal blood flow is compromised). NSAID inhibition of COX reduces these prostaglandins, potentiating ADH-mediated water retention, decreasing sodium excretion, and causing vasoconstriction of renal vasculature. These effects collectively cause sodium and water retention, oedema, and hypertension. NSAIDs also blunt the response to antihypertensive drugs (particularly ACEi and diuretics).

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.