Inhibition of ganglionic long-term potentiation decreases blood pressure in spontaneously hypertensive rats.
Long-term potentiation of sympathetic ganglia (gLTP), a unique form of synaptic plasticity, is serotonin dependent and can be blocked with 5-HT3 receptor antagonists. Long-lasting enhancement of the basal tone of ganglionic transmission (as with gLTP) is expected to result in sustained increase in peripheral resistance that would lead to elevated blood pressure. We examined the possibility that in sympathetic ganglia, gLTP may be involved in the expression of stress-induced (neurogenic) form of hypertension. High blood pressure in spontaneously hypertensive rat (SHR), known to show exaggerated cardiovascular defense reactions to environmental stimuli, is partly due to a neurogenic factor. Chronic treatment of SHR and their normotensive counterpart, the Wistar Kyoto (WKY) rats with the 5-HT3 receptor antagonist tropisetron (ICS; 5 mg/kg/day), caused a marked decrease in the blood pressure of the SHR but not of WKY rats. Increasing the daily dose of ICS cumulatively (7 and 10 mg/kg) did not result in significant additional decrease in blood pressure of SHR, indicating that the drug blocks only the neurogenic component of hypertension in the SHR. electrophysiological procedures for indirectly testing for the presence of gLTP in ganglia excised from SHR suggest that gLTP has been previously expressed in these ganglia in vivo. This contrasts with the absence of gLTP in ganglia from normotensive rats. The results support contribution of gLTP to the expression of neurogenic hypertension.
Alkadhi
K A
KA
Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas 77204-5515, USA. kalkadhi@uh.edu
Otoom
S A
SA
Tanner
F L
FL
Sockwell
D
D
Hogan
Y H
YH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005724:Ganglia / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy; D007211:Indoles / Q000627:therapeutic use; D017774:Long-Term Potentiation / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D013045:Species Specificity; D013997:Time Factors; D000077526:Tropisetron
D007211:Indoles; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D009569:Nitric Oxide; D000077526:Tropisetron