Essential Oil of Croton nepetaefolius Decreases Blood Pressure through an Action upon Vascular Smooth Muscle: Studies in DOCA-Salt Hypertensive Rats

Abstract

Experiments tested the hypothesis that hypotensive effects of intravenous (i.v.) treatment with the essential oil of Croton nepetaefolius (EOCN) result from its vasodilatory effects directly upon vascular smooth muscle. In both deoxycorticosterone-acetate (DOCA)-salt hypertensive and uninephrectomised control, conscious rats, i.v. bolus injections of EOCN (1 to 50 mg/kg) decreased mean aortic pressure (MAP) and heart rate (HR) in a dose-related manner. Treatment with DOCA-salt significantly enhanced EOCN-induced decreases in MAP without affecting bradycardia. Likewise, both maximal percent and absolute decreases in MAP elicited by i.v. hexamethonium (30 mg/kg), a ganglion blocker, were significantly greater in DOCA-salt hypertensive than in control rats. In DOCA-salt hypertensive rats, i.v. pretreatment with hexamethonium (30 mg/kg) reduced the bradycardia elicited by EOCN (50 mg/kg) without affecting the enhancement of EOCN-induced hypotension. In isolated thoracic aorta preparations from DOCA-salt hypertensive rats, EOCN (1 - 300 μg/ml) induced a concentration-dependent reduction of phenylephrine-induced contraction. Arteries from DOCA rats showed increased sensitivity to EOCN, as evidenced by the significant decrease in the IC₅₀ for EOCN-induced reduction of phenylephrine-induced contraction (16.4 ± 3.6 vs. 112.9 ± 23.4 μg/ml in uninephrectomised controls). These results show that i.v. treatment with EOCN dose-dependently decreases blood pressure in conscious DOCA-salt hypertensive rats, and this action is enhanced when compared with uninephrectomised controls. This enhancement appears to be related mainly to an increase in EOCN-induced vascular smooth muscle relaxation rather than to enhanced sympathetic nervous system activity in this hypertensive model. Thus, the hypothesis that EOCN may be a direct vasorelaxant agent is supported by the results of the present study.

Croton nepetaefolius - Euphorbiaceae - essential oil - cardiovascular effects - isolated thoracic aorta - DOCA-salt hypertension - conscious rat

References

• 1 Ducke  A.. Estudos botânicos no Ceará.  An. Acad. Bras. Cienc.. 1959;;  31 7
• 2 Craveiro  A A,, Rodrigues  A S,, Andrade  C HS,, Matos  F JA,, Alencar  J W,, Machado  M IL.. Volatile constituents of Brazilian Euphorbiaceae-genus Croton. .  J. Nat. Prod.. 1981;;  44 602-8
• 3 Leal-Cardoso  J H,, Fonteles  M C.. Pharmacological effects of essential oils of plants of northeast of Brazil.  An. Acad. Bras. Cienc.. 1999;;  71 207-13
• 4 Craveiro  A A,, Andrade  C HS,, Matos  F JA,, Alencar  J W,, Dantas  T NC.. Fixed and volatile constituents of Crotonnepetaefolius. .  J. Nat. Prod.. 1980;;  43 756-7
• 5 Lemos  T LG,, Monte  F LQ,, Guimarães  A M.. Composição química e atividade antimicrobiana de óleo essential de Croton nepetaefolius. Simpósio de Plantas Medicinais do Brasil,. Curitiba, PR, Brazil; 1992: 103
• 6 Magalhães  P JC,, Criddle  D N,, Tavares  R A,, Melo  E M,, Mota  T L,, Leal-Cardoso  J H.. Intestinal myorelaxant and antispasmodic effects of the essential oil of Croton nepetaefolius and its constituents cineole, methyl-eugenol and terpineol.  Phytother. Res.. 1998;;  12 172-7
• 7 Lahlou  S,, Leal-Cardoso  J H,, Magalhães  P JC,, Coelho-de-Souza  A N,, Pinto Duarte  G.. Cardiovascular effects of the essential oil of Croton nepetaefolius in rats: role of the autonomic nervous system.  Planta Med.. 1999;;  65 553-7
• 8 Craveiro  A A,, Matos  F JA,, Alencar  J W.. Simple and inexpensive steam-generator for essential oils extraction.  J. Chem. Educ.. 1976;;  53 562
• 9 Craveiro  A A,, Fernandes  G A,, Andrade  C HS,, Matos  F JA,, Alencar  J W,, Machado  M IL.. Óleos essencias de plantas de nordeste. Edições UFC,. Fortaleza, CE, Brazil; 1981;: 103
• 10 Sapru  H N,, Gonzalez  E R,, Krieger  A J.. Greater splanchnic nerve activity in the rat.  Brain Res. Bull.. 1982;;  8 267-72
• 11 Nagahama  S,, Chen  Y F,, Oparil  S.. Enhanced depressor effect of bromocriptine in the DOCA-salt hypertensive rat.  Am. J. Physiol.. 1985;;  249 H64-70
• 12 Lahlou  S,, Pinto Duarte  G.. Hypotensive action of bromocriptine in the DOCA-salt hypertensive rat: contribution of spinal dopamine receptors.  Fundam. Clin. Pharmacol.. 1998;;  12 599-606
• 13 Lahlou  S,, Pinto Duarte  G,, Demenge  P.. Central dopaminergic origin of bromocriptine induced tachycardia in normotensive rats.  Cardiovasc. Res.. 1993;;  27 2022-7
• 14 Lahlou  S,, Pinto Duarte  G.. Bromocriptine-induced tachycardia in conscious rats: blunted response following isoproterenol pretreatment for 5 days.  Acta Physiol. Pharmacol. Ther. Latinoam.. 1998;;  48 165-74
• 15 Kopin  I J,, Lake  R C,, Ziegler  M.. Plasma levels of norepinephrine.  Ann. Intern. Med.. 1978;;  88 671-80