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RGS2 expression and aldosterone: renin ratio modulate response to drug therapy in hypertensive patients

Semplicini, Andrea; Strapazzon, Giacomo; Papparella, Italia; Sartori, Michelangelo; Realdi, Anna; Macchini, Luisa; Calò, Lorenzo A; Ceolotto, Giulio

doi: 10.1097/HJH.0b013e328339930f
Original papers: Therapeutic aspects

Objective RGS2 (regulators of G-protein signalling) is a negative regulator of Gαq protein signalling, which mediates the action of several vasoconstrictors. Low RGS2 expression increases G-protein-coupled signalling in hypertensive patients. The aim of the present study was to correlate RGS2 expression in peripheral blood mononuclear cells (PBMs) with response to antihypertensive therapy in never-treated patients with essential hypertension.

Methods and design RGS2 expression was measured by real-time quantitative RT-PCR in peripheral blood mononuclear cells (PBMs) from 102 essential hypertensives. The diagnosis of essential hypertension was based on all clinically required tests, including the captopril suppression test. Antihypertensive treatment was given in accordance to international guidelines. End-point of the study was systolic blood pressure (BP) less than 140 mmHg and diastolic BP less than 90 mmHg with three or less different antihypertensive agents, which identified responders to treatment. Resistant hypertension was defined as the failure to control systolic and/or diastolic BP despite at least three different classes of antihypertensive agents, including a diuretic.

Results During follow-up, 85 (83%) patients reached the end point (responders). Resistant hypertensives (n = 17, 17%) were older, had higher baseline BP, plasma aldosterone and aldosterone: renin ratio (ARR) and lower plasma renin activity than patients who reached the end point. RGS2 was negatively correlated to systolic BP at enrolment and significantly lower in PBMs from resistant hypertensives in comparison with patients that reached BP goal. According to logistic regression analysis, high RGS2 expression was predictor of reaching BP goal, whereas high ARR after captopril, age and systolic pressure at enrolment were predictor of resistant hypertension.

Conclusion RGS2 expression affects the response to antihypertensive treatment. Reduced RGS2 expression contributes to resistance to antihypertensive agents through poor negative feedback on the effects of aldosterone and of other vasoactive agents.

Clinica Medica 4, Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy

Received 26 August, 2009

Revised 21 November, 2009

Accepted 9 December, 2009

Correspondence to Professor Andrea Semplicini, MD, UOC Medicina Generale, Ospedale SS. Giovanni e Paolo, Campo SS. Giovanni e Paolo, Castello 6777 – I-30122 Venice, Italy Tel: +39 041 5294360; fax: +39 041 5294651; e-mail: andrea.semplicini@ulss12.ve.it or andrea.semplicini@unipd.it

© 2010 Lippincott Williams & Wilkins, Inc.