Participation of central G‐alpha i2‐subunit proteins in blood pressure regulation and in countering salt‐sensitive hypertension

Abstract

These studies tested the hypothesis that central Gai/o protein pathways are involved in mediating the cardiovascular depressor responses to central a2‐adrenoceptor activation and in countering the development of hypertension to a high NaCl challenge.MethodsThe a2‐agonist guanabenz (50 μg) was administered by intracerebroventricular (i.c.v.) injection to conscious instrumented Sprague‐Dawley (SD) rats pre‐treated (24‐h) i.c.v. with saline or oligodeoxynucleotides (ODN) against Gai1,i2, i3 and ao subunits (25 μg/each). Mean arterial pressure (MAP) and heart rate were recorded and urine collected for 150‐min (10‐min periods). Separate animals were implanted with miniosmotic pumps delivering i.c.v. Gai2 ODN (25 μg/day) and maintained on normal 0.4% NaCl (NS) or high 8% NaCl (HS) chow for 21‐days prior to study.ResultsIn vehicle pretreated SD rats on NS, i.c.v. guanabenz elicited bradycardia, hypotension, diuresis and natriuresis. Selective central down‐regulation of Gai1, i2, i3 or Gao protein did not alter bradycardic or diuretic responses to i.c.v. guanabenz. Gai2 protein down‐regulation prevented the hypotension (peak δMAP [mmHg]; guanabenz, ‐19±2 vs. Gai2 ODN + guanabenz, ‐3±2, P<0.05) and natriuresis to guanabenz (peak δUNaV [ μeq/min]; guanabenz, 7.6±0.8 vs. Gai2 ODN + guanabenz, 2.2±1, P<0.05). When infused (21‐day) with i.c.v. Gai2 ODN, SD rats maintained on HS developed hypertension (MAP [mmHg]; NS + Gai2 ODN, 129±2 vs. HS + Gai2 ODN, 147±3, P<0.05).ConclusionCentral Gαi2 protein‐gated pathways mediate the hypotensive and natriuretic responses to i.c.v. guanabenz. Further, these data suggest a previously unknown novel role for central Gαi2 protein pathways in preventing the development of salt‐sensitive hypertension. DK43337, HL 071212, AHA 0855293E, P20 RR018766