Influence of pertussis toxin pretreatment on the development of L-NAME-induced hypertension.
High blood pressure (BP) of L-NAME hypertensive rats is maintained not only by the absence of nitric oxide (NO)-dependent vasodilatation but also by the enhancement of both sympathetic and angiotensin II-dependent vasoconstriction. The aim of the present study was to evaluate the role of inhibitory G (G(i)) proteins, which are involved in tonic sympathetic vasoconstriction, in the pathogenesis of NO-deficient hypertension. We therefore studied BP response to chronic L-NAME administration (60 mg/kg/day for 4 weeks) in rats in which the in vivo inactivation of G(i) proteins was induced by injection of pertussis toxin (PTX, 10 microg/kg i.v.). The impairment of sympathetic vasoconstriction due to PTX-induced G(i) protein inactivation prevents the full development of NO-deficient hypertension because BP of PTX-treated rats subjected to chronic L-NAME administration did not reach hypertensive values. Nevertheless, chronic NO synthase inhibition per se is capable to increase moderately BP even in PTX-treated rats. Our data suggest that the sympathetic vasoconstriction is essential for the development of established NO-deficient hypertension.
Zicha
J
J
Institute of Physiology Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic. zicha@biomed.cas.cz
Kunes
J
J
Vranková
S
S
Jendeková
L
L
Dobešová
Z
Z
Pintérová
M
M
Pecháňová
O
O
D000818:Animals; D004195:Disease Models, Animal; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D037342:Pertussis Toxin; D051381:Rats; D017208:Rats, Wistar
D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019331:NG-Nitroarginine Methyl Ester