Leptin antagonist reverses hypertension caused by leptin overexpression, but fails to normalize obesity-related hypertension.
OBJECTIVE
The present study employed a rat leptin antagonist to evaluate the role of elevated leptin in obesity-associated hypertension.


METHODS
First, leptin was overexpressed in the hypothalamus of lean rats for 155 days through the administration of a recombinant adeno-associated viral-mediated central vector-encoding leptin. Then a leptin antagonist was infused intracerebroventricularly for 14 days. In a second experiment, rats were fed with a high-fat diet or chow for 5 months, then the leptin antagonist was infused intracerebroventricularly for 14 days.


RESULTS
Hypothalamic overexpression of leptin elevated blood pressure by 18 mmHg, but 14-day central infusion of the leptin antagonist reversed leptin-induced hypertension. High-fat feeding increased blood pressure (by approximately 8-9 mmHg) and tyrosine hydroxylase activity (by 76%) in superior cervical ganglia compared with chow feeding. Leptin antagonist infusion accelerated weight gain, food intake, and adiposity in high-fat-fed rats compared with chow-fed rats, and tyrosine hydroxylase activity was also reversed in the superior cervical ganglia. Elevated mean arterial pressure was not affected, although there was a small decrease in heart rate in both chow and high-fat-fed groups.


CONCLUSIONS
Central overexpression of leptin leads to hypertension that can be reversed by a leptin antagonist. In contrast, this leptin antagonist does not reverse the high-fat feeding-induced elevation of blood pressure, even though there is apparent blockade of other leptin-mediated metabolic and sympatho-excitatory responses.
Tümer
Nihal
N
Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida, USA. ntumer@ufl.edu
Erdös
Benedek
B
Matheny
Michael
M
Cudykier
Idan
I
Scarpace
Philip J
PJ
D000818:Animals; D000229:Dependovirus / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage; D015870:Gene Expression; D005822:Genetic Vectors; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007031:Hypothalamus / Q000503:physiopathology; D007276:Injections, Intraventricular; D020738:Leptin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D008297:Male; D016297:Mutagenesis, Site-Directed; D009765:Obesity / Q000150:complications; D010766:Phosphorylation; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
D004041:Dietary Fats; D020738:Leptin; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat