RGS2 expression and aldosterone: renin ratio modulate response to drug therapy in hypertensive patients.
OBJECTIVE
RGS2 (regulators of G-protein signalling) is a negative regulator of Galphaq 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
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 enrollment 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.


CONCLUSIONS
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.
Semplicini
Andrea
A
Clinica Medica 4, Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy.
Strapazzon
Giacomo
G
Papparella
Italia
I
Sartori
Michelangelo
M
Realdi
Anna
A
Macchini
Luisa
L
Calò
Lorenzo A
LA
Ceolotto
Giulio
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D015331:Cohort Studies; D004351:Drug Resistance; D025461:Feedback, Physiological; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020710:RGS Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D012083:Renin / Q000097:blood*; D055815:Young Adult
D000959:Antihypertensive Agents; D020710:RGS Proteins; C087182:RGS2 protein, human; D012333:RNA, Messenger; D000450:Aldosterone; D012083:Renin