The Labdane Ent-3-Acetoxy-Labda-8(17), 13-Dien-15-Oic Decreases Blood Pressure In Hypertensive Rats.
BACKGROUND
Labdane-type diterpenes induce lower blood pressure via relaxation of vascular smooth muscle; however, there are no studies describing the effects of labdanes in hypertensive rats.


OBJECTIVE
The present study was designed to investigate the cardiovascular actions of the labdane-type diterpene ent-3-acetoxy-labda-8(17), 13-dien-15-oic acid (labda-15-oic acid) in two-kidney 1 clip (2K-1C) renal hypertension.


METHODS
Vascular reactivity experiments were performed in aortic rings isolated from 2K-1C and normotensive (2K) male Wistar rats. Nitrate/nitrite (NOx) measurement was performed in aortas by colorimetric assay. Blood pressure measurements were performed in conscious rats.


RESULTS
Labda-15-oic acid (0.1-300 µmol/l) and forskolin (0.1 nmol/l - 1 µmol/l) relaxed endothelium-intact and endothelium-denuded aortas from both 2K-1C and 2K rats. Labda-15-oic acid was more effective at inducing relaxation in endothelium-intact aortas from 2K pre-contracted with phenylephrine when compared to the endothelium-denuded ones. Forskolin was more potent than labda-15-oic acid at inducing vascular relaxation in arteries from both 2K and 2K-1C rats. Labda-15-oic acid-induced increase in NOx levels was lower in arteries from 2K-1C rats when compared to 2K rats. Intravenous administration of labda-15-oic acid (0.3-3 mg/kg) or forskolin (0.1-1 mg/kg) induced hypotension in conscious 2K-1C and 2K rats.


CONCLUSIONS
The present findings show that labda-15-oic acid induces vascular relaxation and hypotension in hypertensive rats.
Programa de Pós-Graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Janaina A
JA
Simplicio
Núcleo de Pesquisa em Ciências e Tecnologia, Universidade de Franca, Franca, SP, Brazil.
Marilia R
MR
Simão
Núcleo de Pesquisa em Ciências e Tecnologia, Universidade de Franca, Franca, SP, Brazil.
Sergio R
SR
Ambrosio
Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
Carlos R
CR
Tirapelli
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D005576:Colforsin / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000032:analysis; D010656:Phenylephrine / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
C000593534:3-acetoxy-labda-8(17),13-dien-15-oic acid; D004224:Diterpenes; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D005576:Colforsin; D010656:Phenylephrine; D009569:Nitric Oxide