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Anti-epileptic drug gabapentin decreases blood pressure through the attenuation of sympathetic nerve transmission


Our study reveals an important role of sympathetic nervous system in blood pressure lowering by acute administration of gabapentin in spontaneously hypertensive rats (SHR) which is the most widely used model of human hypertension.

Gabapentin (GBP) is an anticonvulsant drug used for the treatment of epilepsy and it is also often used as analgesic in the treatment of chronic neuropathic pain. Gabapentin acts as an inhibitor of voltage-dependent calcium channels (VDCCs) containing the auxiliary α2δ subunit. VDCCs play important role in blood pressure regulation of mammals – the elevated vascular smooth muscle tone is mediated via the L-type VDCCs while the augmented activity of sympathetic nervous system via the N-type VDCCs. The sympathetic nervous system plays an important role in the regulation of blood pressure. The increased sympathetic nerve activity has been observed in both hypertensive humans and animal models of hypertension. Our study revealed that acute administration of gabapentin lowered blood pressure and heart rate more in SHR than in normotensive control WKY rats (Fig. 1). Hypotensive effect of gabapentin was accompanied by a reduction of several indirect measures of sympathetic nerve activity. In agreement with previous results, sympathectomy prevented the blood pressure-lowering effect of gabapentin (Fig. 1). These findings suggest that gabapentin administration lowers blood pressure of SHR mainly through the attenuation of sympathetic nerve transmission. Therefore, sympatholytic effect of gabapentin should be considered in patients subjected to gabapentin treatment.

 

Fig. 1 The effects of intravenous application of gabapentin on the mean arterial pressure (MAP) in control non-sympathectomized (Control) or guanethidine-sympathectomized (Sympx) SHR and WKY rats. The vertical dotted lines represent the time of drug administration.

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 2018, vol. 72, 3, p. 676-685 . IF = 6.823 DOI