Effects of Buflomedil on Spontaneous Vasomotion and Mean Arteriolar Internal Diameter in the Hamster Cheek Pouch

Abstract

Intravital microscopy of the hamster cheek pouch microvasculature was used for in vivo studies on the effects of buflomedil, phentolamine (α-adrenergic receptor antagonist) and norepinephrine on the mean internal arteriolar diameter and spontaneous vasomotion. All drugs were applied topically. The vasomotor activity was studied in 125 arterioles (internal diameter range 18.0–62.0 µm) of 34 preparations. Addition of buflomedil (10^–9 to 10^–5M) did not affect the arteriolar diameter significantly (from 100.7 ± 3.5 to 106.4 ± 1.8%, values expressed in percent of the initial diameter as mean ± SE), but increased the vasomotion frequency and amplitude by approximately 20% (from 7.5 ± 0.3 to 9.2 ± 0.2 cpm) and 30% (from 7.3 ± 0.3 to 10.0 ± 0.5 µm), respectively. Phentolamine (10^–9 to 10^–5M) dose-dependently increased the microvascular diameter (from 102.3 ± 1.2 to 139.1 ± 4.3%) and reduced the vasomotion frequency and amplitude (from 8.0 ± 0.3 to 1.9 ± 0.5 cpm and from 9.0 ± 2.1 to 3.1 ± 0.2 µm, respectively). Addition of buflomedil (10^–7M) reduced the vasodilation evoked by phentolamine (from 103.3 ± 0.7 to 127.0 ± 1.5%) and potentiated its depressive effect on vasomotion frequency and amplitude (from 7.6 ± 0.1 to 1.0 ± 0.3 cpm and from 9.0 ± 0.3 to 1.9 ± 0.6 µm, respectively). Norepinephrine (10^–9 to 10^–5M) dose-dependently decreased to arteriolar diameter (from 102.3 ± 0.7 to 69.6 ± 1.6%) and the vasomotion frequency and amplitude (from 8.4 ± 0.2 to 0.4 ± 0.3 emp and from 8.7 ± 0.2 to 0.5 ± 0.4 µm, respectively). Addition of buflomedil (10^–7 M) reduced the vasoconstriction elicited by norepinephrine (from 103.2 ± 0.9 to 82.9 ± 3.9%) and restored the vasomotion frequency and amplitude (from 8.4 ± 0.3 to 7.8 ± 0.4 cpm and from 8.6 ± 0.2 to 7.8 ± 0.3 µm, respectively). The effects observed with buflomedil on the hamster cheek pouch microcirculation suggest a direct action on the smooth muscle excitability and further support its properties as a competitive inhibitor of α-adrenergic receptors and as a weak calcium antagonist.

Effects of a Calcium Antagonist and of the Adrenergic System on Spontaneous Vasomotion and Mean Arteriolar Diameter in the Hamster Cheek Pouch: Influence of Buflomedil

“…The results obtained with prazosin were similar to the ones reported using phentolamine, an a-adrenergic recep tor blocker in the hamster cheek preparation (topical application) [ 13] and in the hamster skin fold preparation (systemic application) [23], Vasomotion was also reduced in the rat skin preparation with the application of phenoxybenzamine, another a-adrenergic receptor blocker [26], Addition of buflomedil significantly potentiated the ef fects of prazosin on the mean internal arteriolar diameter and on vasomotion frequency and amplitude, possibly due to its competitive inhibition of a-adrenergic receptors [27], In our previous study [13], also in the hamster cheek pouch preparation, addition of butlomedil reduced the vasodilation evoked by phentolamine and potentiated its depressive effect on vasomotion frequency and ampli tude. Our results did not agree with the work reported by Intaglietta et al [28], using the hamster skin fold prepara tion and systemic application of phentolamine.…”

“…In this preparation, sponta neous arteriolar vasomotion occurs both regularly and in such a way that it is readily influenced by various changes in the physical and chemical environment of the prepara tion [ 1 ]. The following was found in this preparation [ 13]: (1) buflomedil applied topically after the control period did not affect the arteriolar diameter significantly, but increased vasomotion frequency and amplitude by ap proximately 20 and 30%, respectively; (2) phentolamine (a-adrenergic receptor blocker) dose-dependently in…”

“…Addition of buflomedil to the superfusion solution after the control period increased vasomotion frequency and amplitude by 20 and 30%, respectively [13], without any significant changes in mean arteriolar internal diame ter. Spontaneous arteriolar vasomotion most likely origi nates from the intrinsic ability of vascular smooth muscle cells to depolarize spontaneously, Ca2+ ions thus being mobilized and initiating contraction.…”

Effect of prolonged pressure on flowmotion: An Investigation Using an in vivo Rat Model

“…Although the incidence of vasomotion and flowmotion has been analyzed in a variety of different tissues [19,20], the results of these studies are still inconsistent. The arteriolar rhythmic diameter changes have been previously characterized as a feature of the physiological [21] or pathophysiological conditions of the microvasculature [19,22].…”

Rapid HPLC measurement of buflomedil in plasma in poisoning cases

“…Buflomedil hydrochloride [2', 4', 6'-trimethoxy-4-(pyrrolidinyl)butyrophenone hydrochloride] is a vasoactive agent: it is used chiefly to treat peripheral vascular disease and to a lesser extent for cerebrovascular arterial disease (Clissold et al, 1987;Bouskela and Cyrino, 1994). Many intoxications involving buflomedil have been described (Piriou et al, 1995;Tracqui et al, 1995;Legras et al, 1996).…”