Synaptic plasticity in sympathetic ganglia from acquired and inherited forms of ouabain-dependent hypertension.
Altered sympathetic nervous system activity has been implicated often in hypertension. We examined short-term potentiation [posttetanic potentiation (PTP)] and long-term potentiation (LTP) in the isolated superior cervical ganglia (SCG) from Sprague-Dawley (SD) rats given vehicle, digoxin, or ouabain by subcutaneous implants as well as in animals with ouabain-induced hypertension (OHR), and inbred Baltimore ouabain-resistant (BOR) and Baltimore ouabain-sensitive (BOS) strains of rats. Postganglionic compound action potentials (CAP) were used to determine PTP and LTP following a tetanic stimulus (20 Hz, 20 s). Baseline CAP magnitude was greater in ganglia from OHR than in vehicle-treated SD rats before tetanus, but the decay time constant of PTP was significantly decreased in OHR and in rats infused with digoxin that were normotensive. In hypertensive BOS and OHR, the time constants for the decay of both PTP and LTP (t(L)) were increased and correlated with blood pressure (slope = 0.15 min/mmHg, r = 0.52, P < 0.047 and 6.7 min/mmHg, r = 0.906, P < 0.0001, respectively). In BOS and OHR, t(L) (minutes) was 492 +/- 40 (n = 7) and 539 +/- 41 (n = 5), respectively, and differed (P < 0.05) from BOR (257 +/- 48, n = 4), SD vehicle rats (240 +/- 18, n = 4), and captopril-treated OHR (370 +/- 52, n = 5). After the tetanus, the CAP at 90 min in BOS and OHR SCG declined less rapidly vs. SD vehicle rats or BOR. Captopril normalized blood pressure and t(L) in OHR. We conclude that the duration of ganglionic LTP and blood pressure are tightly linked in ouabain-dependent hypertension. Our results favor the possibility that enhanced duration of LTP in sympathetic neurons contributes to the increase in sympathetic nerve activity in ouabain-dependent hypertension and suggest that a captopril-sensitive step mediates the link of ouabain with LTP.
Aileru
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AA
Department of Pharmacology, University of Maryland School of Medicine, 685 West Baltimore St., Baltimore, MD 21201-1559, USA.
De Albuquerque
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Hamlyn
J M
JM
Manunta
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P
Shah
J R
JR
Hamilton
M J
MJ
Weinreich
D
D
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004077:Digoxin / Q000494:pharmacology; D004195:Disease Models, Animal; D004594:Electrophysiology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000502:physiology*
D010042:Ouabain; D004077:Digoxin