Effects of gamma-vinyl GABA (vigabatrin) on blood pressure and body weight of hypertensive and normotensive rats.
Inactivation of GABA was inhibited by gamma-vinyl GABA (GVG) and the effects of the increased GABA level in the brain on blood pressure and body weight of spontaneously hypertensive rats (SHR) and normotensive rats (WKY) were investigated. When started at the age of 8 weeks or 5 weeks, treatment of SHR and WKY with GVG (150 mg/kg, s.c.) for several weeks did not influence systolic blood pressure. In 1-week old SHR, treatment with GVG (up to 150 mg/kg, s.c.) abolished the rise in blood pressure until animals were 8 weeks old. Thereafter, arterial blood pressure started to increase but it remained distinctly lower than that in untreated animals. When started at the age of 1 week, treatment with GVG for 7 weeks did not influence arterial blood pressure in WKY. GVG delayed increase in body weight in SHR and WKY, irrespective of their age. GVG greatly increased GABA levels in the hypothalamus, frontal cortex, brainstem and rest of the brain in both WKY and SHR. It is concluded that an increase in the GABA level in the brain leads to a delay in the development of hypertension in young SHR. Hence, development of genetic hypertension seems to be susceptible to activation of the GABAergic system in a very early critical phase only.
Singewald
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Institut für Pharmakodynamik und Toxikologie, Universität Innsbruck, Austria.
Pfitscher
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A
Philippu
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A
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000614:Aminocaproates / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism*
D000614:Aminocaproates; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin