The Labdane Ent-3-Acetoxy-Labda-8(17), 13-Dien-15-Oic Decreases Blood Pressure In Hypertensive Rats

Simplicio, Janaina A.; Simão, Marilia R.; Ambrosio, Sergio R.; Tirapelli, Carlos R.

doi:10.5935/abc.20160058

Acessibilidade / Reportar erro

Brasil

Arquivos Brasileiros de Cardiologia

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Original Articles • Arq. Bras. Cardiol. 106 (6) • June 2016 • https://doi.org/10.5935/abc.20160058 copy

The Labdane Ent-3-Acetoxy-Labda-8(17), 13-Dien-15-Oic Decreases Blood Pressure In Hypertensive Rats

Authorship SCIMAGO INSTITUTIONS RANKINGS

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.

Keywords:
Labdane; Vascular Relaxation; Diterpene; Forskolin; Renovascular Hypertension

	2K		2K-1C
	Basal	After 6 weeks	Basal	After 6 weeks
MAP	104.3 ± 2.0	100.9 ± 1.6	105.7 ± 1.1	161.3 ± 10.4^a a Compared to respective basal values (p < 0.05, paired Student's t test). MAP: mean arterial pressure; DBP: diastolic blood pressure; SBP: systolic blood pressure.
DBP	92.5 ± 1.8	89.8 ± 1.3	96.3 ± 1.1	138.4 ± 11.6^a a Compared to respective basal values (p < 0.05, paired Student's t test). MAP: mean arterial pressure; DBP: diastolic blood pressure; SBP: systolic blood pressure.
SBP	127.9 ± 2.8	123.2 ± 2.9	124.6 ± 1.9	207.0 ± 9.2^a a Compared to respective basal values (p < 0.05, paired Student's t test). MAP: mean arterial pressure; DBP: diastolic blood pressure; SBP: systolic blood pressure.

	Pre-contractile agent	2K		2K-1C
	Pre-contractile agent	E+ (E_max)	E- (E_max)	E+ (E_max)	E- (E_max)
Labda-15-oic acid	Phenylephrine	93.7 ± 6.8 (7)	79.2 ± 1.8 (6)	99.0 ± 7.4 (7)	88.8 ± 6.6 (6)
Labda-15-oic acid	KCl	96.4 ± 4.4 (7)	83.6 ± 6.6 (6)	103.9 ± 3.8 (7)	87.3 ± 7.4 (8)
Forskolin	Phenylephrine	110.7 ± 5.3 (7) ^a a Compared to labda-15-oic acid in aortas pre-contracted with phenylephrine from 2K and 2K-1C rats;	104.0 ± 5.62a (6)	118.8 ± 5.2 (6) ^a a Compared to labda-15-oic acid in aortas pre-contracted with phenylephrine from 2K and 2K-1C rats;	107.7 ± 8.0 (6) ^a a Compared to labda-15-oic acid in aortas pre-contracted with phenylephrine from 2K and 2K-1C rats;
Forskolin	KCl	92.6 ± 3.9 (6)	87.8 ± 3.9 (5)	105.9 ± 3.3 (6)	93.2 ± 7.1 (6)
		E+ (pD₂)	E- (pD₂)	E+ (pD₂)	E- (pD₂)
Labda-15-oic acid	Phenylephrine	4.8 ± 0.06 (7)	4.1 ± 0.04 (6)^b b Compared to respective group in E+ aortas from 2K and 2K-1C rats;	4.8 ± 0.11 (7)	4.9 ± 0.08(6)
Labda-15-oic acid	KCl	4.6 ± 0.08 (7)	4.3 ± 0.06 (6)	4.8 ± 0.10 (7)	4.5 ± 0.08 (8)
Forskolin	Phenylephrine	7.5 ± 0.21 (7) ^c c Compared to labda-15-oic acid in aortas pre-contracted with phenylephrine or KCl from 2K and 2K-1C rats (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test).	6.9 ± 0.17(6) ^b b Compared to respective group in E+ aortas from 2K and 2K-1C rats; ,^c c Compared to labda-15-oic acid in aortas pre-contracted with phenylephrine or KCl from 2K and 2K-1C rats (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test).	8.0 ± 0.10 (6) ^c c Compared to labda-15-oic acid in aortas pre-contracted with phenylephrine or KCl from 2K and 2K-1C rats (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test).	7.3 ± 0.14(6) ^b b Compared to respective group in E+ aortas from 2K and 2K-1C rats; ,^c c Compared to labda-15-oic acid in aortas pre-contracted with phenylephrine or KCl from 2K and 2K-1C rats (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test).
Forskolin	KCl	7.0 ± 0.16 (6) ^c c Compared to labda-15-oic acid in aortas pre-contracted with phenylephrine or KCl from 2K and 2K-1C rats (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test).	7.0 ± 0.15(5) ^c c Compared to labda-15-oic acid in aortas pre-contracted with phenylephrine or KCl from 2K and 2K-1C rats (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test).	7.3 ± 0.20 (6) ^c c Compared to labda-15-oic acid in aortas pre-contracted with phenylephrine or KCl from 2K and 2K-1C rats (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test).	7.0 ± 0.12 (6) ^c c Compared to labda-15-oic acid in aortas pre-contracted with phenylephrine or KCl from 2K and 2K-1C rats (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test).

	MAP (mmHg)
	Before	After	ΔMAP	%ΔMAP
Labda-15-oic acid 2K
Vehicle	103.5 ± 6.7 (5)	98.9 ± 7.0	4.6 ± 2.4	4.4 ± 2.3
Labda-15-oic acid (0.3 mg/kg)	100.5 ± 5.5 (5)	96.3 ± 8.4	4.2 ± 3.3	4.8 ± 3.8
Labda-15-oic acid (1 mg/kg)	99.8 ± 6.2 (5)	70.6 ± 15.6	29.2 ± 12.7	30.3 ± 13.6
Labda-15-oic acid (3 mg/kg)	98.5 ± 6.4 (5)	48.6 ± 12.4^a a Significant difference compared to baseline, before drug infusion (p < 0.05, paired Student’s t test).	49.9 ± 8.5^b b Compared with vehicle (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test). MAP: mean arterial pressure.	53.6 ± 10.9 ^b b Compared with vehicle (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test). MAP: mean arterial pressure.
Labda-15-oic acid 2K-1C
Vehicle	163.7 ± 15.2 (6)	159.3 ± 16.2	4.4 ± 3.0	3.0 ± 2.3
Labda-15-oic acid (0.3 mg/kg)	161.6 ± 15.8 (6)	154.0 ± 16.5	7.6 ± 3.3	5.2 ± 2.5
Labda-15-oic acid (1 mg/kg)	160.0 ± 15.6 (6)	148.0 ± 15.7	12.0 ± 3.6	7.9 ± 2.7
Labda-15-oic acid (3 mg/kg)	160.2 ± 15.8 (6)	109.7 ±19.2^a a Significant difference compared to baseline, before drug infusion (p < 0.05, paired Student’s t test).	50.5 ± 9.9^b b Compared with vehicle (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test). MAP: mean arterial pressure.	33.8 ± 8. 4^b b Compared with vehicle (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test). MAP: mean arterial pressure.
Forskolin 2K
Vehicle	113.9 ± 3.0 (5)	107.5 ± 4.3	6.4 ± 1.7	5.7 ± 1.5
Forskolin (0.1 mg/kg)	104.9 ± 4.5 (5)	90.9 ± 5.2^a a Significant difference compared to baseline, before drug infusion (p < 0.05, paired Student’s t test).	14.0 ± 2.7	13.4 ± 2.8
Forskolin (0.3 mg/kg)	108.1 ± 5.0 (5)	75.8 ± 10.8^a a Significant difference compared to baseline, before drug infusion (p < 0.05, paired Student’s t test).	32.3 ± 10.0^b b Compared with vehicle (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test). MAP: mean arterial pressure.	29.9 ± 9.6^b b Compared with vehicle (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test). MAP: mean arterial pressure.
Forskolin (1 mg/kg)	107.4 ± 4.0 (5)	77.0 ± 3.1^a a Significant difference compared to baseline, before drug infusion (p < 0.05, paired Student’s t test).	30.4 ± 5.2^b b Compared with vehicle (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test). MAP: mean arterial pressure.	27.9 ± 3.8^b b Compared with vehicle (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test). MAP: mean arterial pressure.
Forskolin 2k-1C
Vehicle	169.1 ± 12.8 (5)	163.3 ± 15.1	5.8 ± 4.6	3.7 ± 2.5
Forskolin (0.1 mg/kg)	170.4 ± 16.6 (5)	153.2 ± 12.9^a a Significant difference compared to baseline, before drug infusion (p < 0.05, paired Student’s t test).	17.2 ± 6.1	9.4 ± 3.1
Forskolin (0.3 mg/kg)	167.6 ± 16.3 (5)	130.9 ± 12.4^a a Significant difference compared to baseline, before drug infusion (p < 0.05, paired Student’s t test).	36.7 ± 5.7^b b Compared with vehicle (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test). MAP: mean arterial pressure.	21.7 ± 2.5^b b Compared with vehicle (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test). MAP: mean arterial pressure.
Forskolin (1 mg/kg)	166.0 ± 16.9 (5)	97.1 ± 16.0^a a Significant difference compared to baseline, before drug infusion (p < 0.05, paired Student’s t test).	68.9 ± 8.5^b b Compared with vehicle (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test). MAP: mean arterial pressure.	42.4 ± 6.2^b b Compared with vehicle (p < 0.05, ANOVA followed by Newman-Keuls multiple comparison test). MAP: mean arterial pressure.

Sociedade Brasileira de Cardiologia - SBC Avenida Marechal Câmara, 160, sala: 330, Centro, CEP: 20020-907, (21) 3478-2700 - Rio de Janeiro - RJ - Brazil, Fax: +55 21 3478-2770 - São Paulo - SP - Brazil
E-mail: revista@cardiol.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] Mailing Address: Carlos Renato Tirapelli, Universidade de São Paulo - Escola de Enfermagem de Ribeirão Preto - Avenida Bandeirantes 3900, Postal Code 14040-902, Ribeirão Preto, SP - Brazil. E-mail: crtirapelli@eerp.usp.br, crtlilo@hotmail.com