ABSTRACT
Abstract 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. Conclusion: The present findings show that labda-15-oic acid induces vascular relaxation and hypotension in hypertensive rats.
Resumo Fundamento: Diterpenos do tipo labdano induzem uma queda da pressão arterial por meio do relaxamento do músculo liso vascular; todavia, não há estudos que descrevam os efeitos de labdanos em ratos hipertensos. Objetivo: O presente estudo foi desenvolvido para investigar as ações cardiovasculares do labdano ácido ent-3-acetóxi-labda-8(17),13-dieno-15-óico (labda-15-óico) na hipertensão renal dois rins-1 clipe (2R-1C). Métodos: Foram feitos experimentos de reatividade vascular em anéis aórticos isolados de ratos machos 2R-1C e normotensos (2R). A medição de Nitrato/Nitrito (NOx) foi feita nas aortas por meio de ensaio colorimétrico. As medidas de pressão arterial foram feitas em ratos conscientes. Resultados: O ácido labda-15-óico (0,1 - 300 µmol/l) e a forscolina (0,1 nmol/l - 1 µmol/l) relaxaram as aortas com endotélio intacto e as aortas sem endotélio dos ratos 2R-1C e 2R. O labda-15-óico mostrou-se mais eficaz na indução do relaxamento em aortas com endotélio intacto de 2R pré-contraídas com fenilefrina em comparação àquelas sem endotélio. A forscolina mostrou-se mais potente do que o ácido labda-15-óico na indução do relaxamento vascular nas artérias tanto de ratos 2R-1C quanto de ratos 2R. O aumento dos níveis de NOx induzido pelo ácido labda-15-óico foi menor nas artérias de ratos 2R-1C em comparação a ratos 2R. A administração intravenosa de ácido labda-15-óico (0,3-3 mg/kg) ou forscolina (0,1-1 mg/kg) induziu hipertensão em ratos 2R-1C e 2R conscientes. Conclusão: Os presentes resultados mostram que o labda-15-óico induz relaxamento vascular e hipotensão em ratos hipertensos.
Subject(s)
Animals , Male , Rats , Vasodilator Agents/pharmacology , Blood Pressure/drug effects , Colforsin/pharmacology , Diterpenes/pharmacology , Hypertension, Renovascular/drug therapy , Aorta, Thoracic/drug effects , Phenylephrine/antagonists & inhibitors , Vasoconstrictor Agents/antagonists & inhibitors , Vasodilation/drug effects , Vasodilator Agents/chemistry , Colforsin/chemistry , Rats, Wistar , Disease Models, Animal , Diterpenes/chemistry , Drug Evaluation, Preclinical , Hypertension, Renovascular/physiopathology , Muscle, Smooth, Vascular/drug effects , Nitric Oxide/analysisABSTRACT
The circulatory effects of norepinephrine (4 * g/kg) and phenylephrine (20 */kg) were determined in anesthetized dogs withnormal plasma magnesium and with induced hypermagnesemia. Norepinephrine caused a 24% increased in heart rate by 103% increase in the systemic vascular, resistance index in normomagnesemic dogs, while with hypermagnesemia the variations were of 13% and 1%, respectively. Isoproterenol increased heart rate by 485 and 185 in dogs with normo- and hypermagnesemia, respectively.Phenylephrine increased the systemic vascular resistance index (74%) only in the normomagnesemic state.The effects of all the drugs were significantly defferent (P<0.01), without and with the simultaneous administration of magnesium sulfate (plasma magnesium, 1.3ñ0.2mEq/l and 6.8ñ1.1 mEq/l, respectively).We conclude that acute induced hypermagnesemia antagonizes the circulatory effects of adrenergic stimulation, a fact that may explain its antiarrhythmic and hemodynamic effects during acute myocardial ischemia
Subject(s)
Dogs , Animals , Hemodynamics/drug effects , Isoproterenol/antagonists & inhibitors , Magnesium/blood , Norepinephrine/antagonists & inhibitors , Phenylephrine/antagonists & inhibitors , Calcium/metabolism , Coronary Disease/physiopathologyABSTRACT
Phenylephrine exerted a positive chronotropic and inotropic effect on isolated, spontaneously beating, atria of reserpinised rabbits. Addition of phenoxybenzamine and phentolamine resulted in a depression of control contractile amplitude. Practolol, however, was devoid of this effect. The positive inotropic response to phenylephrine was significantly antagonised by all the three blockers used, while positive chronotropic response was annulled by phentolamine and practolol, but not with phenoxybenzamine. It is, therefore, suggested that phenylephrine exerts its cardiostimulant effects through mediation of both alpha and beta-1 adrenoceptors. A probable mechanism of action could be, that phenylephrine acts on some specific chemical group, shared by alpha and beta1 receptors. This specific group is probably blocked by both alpha and betaceptor antagonists separately, so phenylephrine becomes ineffective in presence of these antagonists.