The role of nitrinergic connections in central cardiovascular responses mediated by physostigmine infused into posterior hypothalamus.
In the last few decades, cholinergic connections located into posterior hypothalamus (PH) have been implicated in the central regulation of blood pressure (BP). Here we investigated the role of nitric oxide (NO) in the blood pressure response elicited by infusion of physostigmine into PH of normotensive rats. In freely moving rats, physostigmine (60-200 nM) produced a dose- and time-dependent elevation of BP which was antagonized by the antimuscarinic drug scopolamine (60 nM) and by L-NAME (100 microM), an inhibitor of NO synthase, both infused into the same site. In contrast, L-arginine (L-Arg; 100 microM), the precursor of NO, and glyceryltrinitrate (GTN; 140 nM), an NO donor, infused into the PH did not affect physostigmine-related pressor response. In rats pre-treated with Escherichia coli lipopolisaccharide (LPS; 0.5 microg i.p. 24h beforehand), however, scopolamine, L-Arg and GTN produced a decrease of BP, an effect antagonized by L-NAME. This suggests that NO only slightly modulates physostigmine-related pressor response elicited into PH of LPS-untreated rats. In contrast, the release of large amounts of NO generated by pre-treating rats with LPS, down-regulates cholinergic connections located at the PH, thus contributing in the central dysregulation of BP which can be found when high circulating endotoxin levels may occur.
Palma
Ernesto
E
Faculty of Pharmacy, University of Catanzaro "Magna Graecia", Roccelletta di Borgia, 88100 Catanzaro, Italy.
Muscoli
Carolina
C
Mancuso
Eliana
E
Sculco
Francesca
F
Sacco
Iolanda
I
Alecce
Wanessa
W
Costa
Nicola
N
Colica
Carmela
C
Cristiano
Dario
D
Rotiroti
Domenicantonio
D
Mollace
Vincenzo
V
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology; D006439:Hemodynamics / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007034:Hypothalamus, Posterior / Q000502:physiology*; D007267:Injections; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010830:Physostigmine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002800:Cholinesterase Inhibitors; D004731:Endotoxins; D008070:Lipopolysaccharides; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D010830:Physostigmine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester