Hemodynamic Response to Gabapentin in Conscious Spontaneously Hypertensive Rats: The Role of Sympathetic Nervous System

0492836 - FGÚ 2019 RIV US eng J - Článek v odborném periodiku
Behuliak, Michal - Bencze, Michal - Polgárová, Kamila - Kuneš, Jaroslav - Vaněčková, Ivana - Zicha, Josef
Hemodynamic Response to Gabapentin in Conscious Spontaneously Hypertensive Rats: The Role of Sympathetic Nervous System.
Hypertension. Roč. 72, č. 3 (2018), s. 676-685. ISSN 0194-911X. E-ISSN 1524-4563
Grant CEP: GA ČR(CZ) GJ16-10349Y; GA ČR(CZ) GP14-16225P; GA MZd(CZ) NV15-25396A
Institucionální podpora: RVO:67985823
Klíčová slova: baroreflex * calcium channels * gabapentin * sympathectomy * sympathetic nervous system
Obor OECD: Cardiac and Cardiovascular systems
Impakt faktor: 7.017, rok: 2018

Ligands of auxiliary (2) subunit of voltage-dependent calcium channels (VDCCs) decrease elevated L-type VDCCs surface expression in arterial myocytes and arterial constriction in spontaneously hypertensive rats (SHR). However, their effect on blood pressure (BP) is unclear. In this study, we investigated the hemodynamic response to acute and chronic administration of gabapentin, a ligand of auxiliary (2) subunit of VDCCs, in adult SHR with established neurogenic hypertension. The acute gabapentin administration lowered BP and heart rate more in conscious SHR than Wistar-Kyoto rats. Both nifedipine (L-type VDCCs blocker) and -conotoxin GVIA (N-type VDCCs blocker) also decreased BP more in SHR, but only gabapentin and -conotoxin GVIA abolished the nitroprusside-induced reflex tachycardia of baroreceptor-heart rate control. Hypotensive effect of gabapentin was accompanied by a reduction of (1) plasma norepinephrine level, (2) depressor response to ganglionic blocker pentolinium, (3) power of low frequency component of systolic BP variability, and (4) pressor response of mesenteric vascular bed to periarterial nerve stimulation, suggesting the decrease of peripheral sympathetic nerve transmission. Moreover, gabapentin effects on BP and baroreflex were absent in sympathectomized rats. In conclusion, the acute (but not chronic) administration of gabapentin lowered BP more in SHR than in Wistar-Kyoto rats. Besides the known L-type VDCCs involvement in the vascular effect of gabapentin, our data revealed the important role of N-type VDCCs in acute gabapentin effect on sympathetic control of BP. Gabapentin-induced changes of sympathetic nerve transmission indicated major hemodynamic mechanism of the acute response to this drug.
Trvalý link: http://hdl.handle.net/11104/0286265