Central but not peripheral G‐alpha i/o protein inhibition potentiates hypertension in hypertensive Dahl salt‐sensitive rats: a protective role for central G‐alpha i/o proteins

Abstract

We have shown that intracerebroventricular (i.c.v.) pre‐treatment of rats with pertussis toxin (PTX) prevents the hypotensive and bradycardic responses to the Gαi/o‐protein coupled receptor ligands, nociceptin/orphanin FQ and clonidine. These studies examined whether central Gαi/o protein inhibition alters blood pressure in hypertensive Dahl salt sensitive (DSS) rats.Methods DSS rats were implanted with radio‐telemetry probes and MAP and HR were continuously monitored. After 1‐week, rats were maintained on 8% NaCl chow for 3 weeks then administered either i.c.v. iso‐saline vehicle (N=6), i.c.v. PTX (1 μg) (N=6), or intraperitoneal (i.p.) PTX (15 μg/kg) (N=6).Results DSS rats on 8% NaCl chow showed a significant increase in MAP (normal chow MAP, 130 ± 2 mmHg; 8% NaCl chow, 164 ± 8 mmHg, P<0.05). In hypertensive DSS rats, central PTX significantly increased MAP (day 4 post i.c.v. PTX; MAP Δ +25 ± 2 mmHg, P<0.05). In contrast, peripheral PTX administration produced a significant hypotension (day 4 post i.p. PTX; MAP Δ −58 ± 9 mmHg, P<0.05).Conclusion In hypertensive DSS rats, endogenous central Gαi/o protein pathways participate in reducing the severity of high NaCl‐induced hypertension. This is in contrast to the role of peripheral Gαi/o proteins, which in these (DSS) and previous studies (spontaneously hypertensive rats) play a pathological role in the maintenance of hypertension. Thus, endogenous central vs. peripheral Gαi/o proteins have differential affects on blood pressure control and potentially in the etiology of hypertension. DK43337, HL 071212, P20 RR018766