Hemodynamic Response to Gabapentin in Conscious Spontaneously Hypertensive Rats
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- baroreflex, calcium channels, gabapentin, sympathectomy, sympathetic nervous system,
- MeSH
- Analgesics pharmacology MeSH
- Calcium Channel Blockers pharmacology MeSH
- Species Specificity MeSH
- Gabapentin pharmacology MeSH
- Hypertension physiopathology MeSH
- Blood Pressure drug effects physiology MeSH
- Nifedipine pharmacology MeSH
- Rats, Inbred SHR MeSH
- Rats, Inbred WKY MeSH
- Heart Rate drug effects physiology MeSH
- Sympathetic Nervous System drug effects physiology MeSH
- Calcium Channels, L-Type metabolism MeSH
- Calcium Channels, N-Type metabolism MeSH
- Consciousness MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Analgesics MeSH
- Calcium Channel Blockers MeSH
- Gabapentin MeSH
- Nifedipine MeSH
- Calcium Channels, L-Type MeSH
- Calcium Channels, N-Type MeSH
Ligands of auxiliary α2δ 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 α2δ 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 ω-conotoxin GVIA (N-type VDCCs blocker) also decreased BP more in SHR, but only gabapentin and ω-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.
References provided by Crossref.org
Altered Balance between Vasoconstrictor and Vasodilator Systems in Experimental Hypertension
