Cardiovascular Effects of Visnagin on Rats

Abstract

The present article describes the effects of visnagin on systolic blood pressure and heart rate in the anaesthetized rat. Intravenous administration of visnagin (0.3 - 5 mg kg⁻¹) produced dose-related decreases in blood pressure with no significative changes in heart rate. Under nitric oxide synthase inhibition (L-NAME, 50 mg kg⁻¹) the hypotensive effects of visnagin (5 mg kg⁻¹) were not affected. Visnagin (5 × 10⁻⁶ M − 10⁻⁴ M) produced a weak decrease in the rate and amplitude of spontaneous contractions in right atria. Visnagin also caused a weak decrease in peak contractile force and the df/dt_max with no significant changes in the time to peak tension or the time for total contraction in left atria driven at a basal rate of 1 Hz. Visnagin (10⁻⁵ M, 5 × 10⁻⁵ M and 10⁻⁴ M) concentration-dependently decreased pressor response to KCl (IC₅₀ = 5.1 ± 2.5 × 10⁻⁵ M) and noradrenaline (IC₅₀ = 2.6 ± 0.9 × 10⁻⁵ M) in rat isolated mesenteric beds. Visnagin (3 × 10 ⁻⁷ M − 10⁻⁴ M) induced a concentration-dependent relaxation of isolated mesenteric arteries contracted by noradrenaline (IC₅₀ = 1.7 ± 0.8 × 10⁻⁵ M). The relaxant effects in the absence of functional endothelium were not significantly different (IC₅₀ = 1.5 ± 0.3 × 10⁻⁵ M, P > 0.05) from those observed in segments with intact endothelium. In conclusion, the main mechanism responsible for the acute hypotensive effect of visnagin is the vasorelaxant response induced by this drug in resistance arteries.

Abbreviations

ANOVA:Analysis of variance

CHAPS:3-[(3-Cholamidopropryl) dimethylammonio]-1-propanesulfonate

df/dt_max:Maximum rate of contraction

DMSO:Dimethyl sulfoxide

IC₅₀:Half-maximal inhibitory concentration

L-NAME:N ^G-nitro-L-arginine methyl ester

PDE:Phosphodiesterase

PSS:Physiological salt solution

S.E.M.:Standard error mean

Key words

Visnagin - Ammi visnaga - Apiaceae - aorta - mesenteric arteries - atria - rat

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