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Abstract
The dried roots of Danshen (Salvia miltiorrhiza) and Sanchi (Panax notoginseng) have been widely used in traditional Chinese medicine for promoting blood circulation as well as various other bodily functions. Here we investigated the effects of a mixture of aqueous extracts of Danshen and Sanchi, named PASEL, on blood pressure and vascular contractility in rats. Orally administered PASEL (62.5 mg/kg and 250 mg/kg, for 5 weeks) lowered the blood pressure of spontaneous hypertensive rats (SHR) but this was not observed in normal Wistar-Kyoto rats (WKR). We then investigated the effects of PASEL on the arterial contraction of the small branches of cerebral arteries (CAs) and large conduit femoral arteries (FAs) in rats. PASEL did not affect high-K (KCl 60 mM)- or phenyleprine (PhE)-induced contracture of FAs. The myogenic response, a reactive arterial constriction in response to increased luminal pressure, of small CA was dose-dependently suppressed by PASEL in SHR as well as control rats. Interestingly, the KCl-induced contraction of small CAs was slowly reversed by PASEL, and this effect was more prominent in SHR than control WKR. PASEL did not inhibit angiotensin-converting enzyme (ACE) activity. These results demonstrated that the antihypertensive effect of PASEL might be primarily mediated by altering the arterial MR, not by direct inhibition of L-type Ca2+ channels or by ACE inhibition.
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Fig. 1.
Effects of PASEL treatment on blood pressure (BP) of SHR and control rats. (A) BP measurements were conducted using tail-cuff methods in WKY control and SHR (n=5, respectively) for five weeks. PASEL was applied daily (62.5 and 250 mg/kg, p.o.) for five weeks. The BP of SHR was lowered from the first week of PASEL application, while not completely normalized to the control level. The mean BP values are indicated in Fig. (B) The BP of each animal was normalized (100%) to the initial level and the mean values are summarized. (C, D) Summary of the heart rates (beat per minute, BPM) and body weights (g).
Fig. 2.
No significant effect of PASEL on high K+- and phenyleprine-induced contraction of large femoral artery. (A, B) Representative traces of isometric contraction of femoral arteries induced by 60 mM KCl (60 K) or 5 μM of phenyleprine (PhE). After confirming the consistent contractile responses to repetitive application of KCl or PhE (left panels), PASEL was applied (right panels). Neither 60 K- nor PhE-induced contraction was affected by pretreatment of the animals with 100 μg/ml PASEL. (C) Summary of the contractile responses in the absence (open bars) or the presence of PASEL (100 μg/ml, closed bars). Contractile responses were normalized (%) to the initial control amplitude. The number of tested arteries is indicated above each bar.
Fig. 3.
Effects of PASEL on MR of rat cerebral arteries. (A) A representative trace of diameter (Din) measured during application of PASEL (1~100 μg/ml) at 80 mmHg in the cerebral artery of WKR. (B) Summary of MR in % scale (see Methods) between WKR and SHR. There was no statistical significance between both groups. (C, D) Summary of the effects of 1~100 μg/ml PASEL on MR of WKR and SHR at 80 mmHg, respectively. Normalized diameters (% values of control Din at 80 mmHg) were averaged. The numbers in parenthesis above each point indicate numbers of tested arteries. (E, F) Summary of the effects of 10~100 μg/ml PASEL on MR of WKR and SHR at 120 mmHg, respectively (∗p value < 0.05).
Fig. 4.
Effects of PASEL on high K+-induced constriction of rat cerebral arteries. (A, B) Representative traces of inner diameter (Din) showing the high K+-constriction and the inhibition by PASEL (1~100 μg/ml) treatment in WKR and SHR. (C, D) Summary of the concentration-dependent effects of PASEL in WKR and SHR, respectively. Changes in Din (ΔDin%) are expressed in percent values versus the extent of high-K+ constriction ΔDin at 40 mmHg as 100%. The extent of dilation by 100 μg/ml PASEL was more prominent in SHR than WKR (p<0.05, # in D).
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