Mechanisms of the vasorelaxant effect of Danshen (Salvia miltiorrhiza) in rat knee joints

The aim of this study is to investigate the mechanisms of the vasorelaxant effect of the crude extract of Salvia miltiorrhiza (family: Labiatae), also known as Danshen, in rat knee joints. Changes in blood flow of rat knee joints were measured in vivo by a laser Doppler perfusion imager. Topical administration of Danshen onto the exposed knee joint blood vessels produced dose-dependent increases in blood flow. Treatment of the rat knee joint with 2 x 1 nmol of atropine, 2 x 0.1 nmol of propranolol, or 2 x 0.1 nmol of a mixture of pyrilamine plus cimitedine produced no change on the vasodilator response to Danshen. However, significant inhibition of the Danshen-induced vasodilator response was observed in knee joints treated with 2 x 100 nmol of N-G-nitro-L-arginine methyl ester (L-NAME), 2 x 100 nmol of flurbiprofen, 2 x 10 nmol of the calcitnonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37), and also in knee joints but had been denervated by capsaicin treatment or by surgery. Intravenous administration of low doses of Danshen (2.5 and 6 mg/kg) did not affect the systemic blood pressure but significantly increased knee joint blood flow, whereas, high doses of Danshen (167 and 381 mg/kg) produced hypotension with concurrent decreases in knee joint blood flow. These findings indicate that the knee joint blood vessels are more sensitive to the relaxant effect of Danshen compared to blood vessels in the general circulation. The vasorelaxant effect of Danshen was found to be partly mediated by CGRP released from sensory nerves, and nitric oxide and prostaglandins also played a part. However, there is no evidence to support a role for muscarinic receptors, adrenoceptors, or histamine receptors. (c) 2005 Elsevier Ireland Ltd. All rights reserved.