title: Sympathetic overactivity prevails over the vascular amplifier phenomena in a chronic kidney disease rat model of hypertension.
abstract: We examined whether increased sympathetic nerve activity (SNA) accounts for enhanced depressor responses to ganglionic blockade in the Lewis polycystic kidney (LPK) model of chronic kidney disease (CKD) or whether it reflects increased vascular responses to vasodilation (vascular amplifier). Under urethane anesthesia, depressor responses to ganglionic blockade (hexamethonium, 0.5-40 mg/kg i.v.), and direct vasodilation (sodium nitroprusside [SNP], 2.5-40 μg/kg i.v. and adenosine, 3-300 μg/kg i.v.) were compared in the LPK with normotensive Lewis and spontaneously hypertensive rats (SHR) (total n = 37). Hexamethonium (8 mg/kg) produced a greater depressor response in the LPK (-51 ± 3 mmHg) compared with Lewis (-31 ± 3 mmHg, P < 0.05) but not SHR (-46 ± 3 mmHg). In LPK, the ratio of the hexamethonium/vasodilator MAP responses was greater when compared with Lewis (hexamethonium/SNP 1.34 ± 0.1 vs. 0.9 ± 0.09 and hexamethonium/adenosine: 2.28 ± 0.3 vs. 1.16 ± 0.1, both P < 0.05) but not SHR. Results for systolic blood pressure (SBP) were comparable. The slope of the relationship between the fall in SBP induced by hexamethonium and normalized low frequency (LFnu) power was also greater in the LPK (17.93 ± 3.26 mmHg/LFnu) compared with Lewis (2.78 ± 0.59 mmHg/LFnu, P = 0.001) and SHR (3.36 ±0.72 mmHg/LFnu, P = 0.003). These results indicate that in the LPK, sympathetic activity predominates over any vascular amplifier effect, supporting increased sympathetic vasomotor tone as a major contributor to hypertension in this model of CKD.
authors.affiliation: The Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Omar Z
authors.initials: OZ
authors.lastname: Ameer
authors.affiliation: The Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Cara M
authors.initials: CM
authors.lastname: Hildreth
authors.affiliation: The Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Phillips
keywords: Chronic kidney disease; ganglion blockade; sympathetic nervous system; vascular amplifier