Involvement of Different Activator Ca2+ in the Rate-Dependent Stretch-Induced Contractions of Canine Basilar Artery.

Abstract

The contractile response of vascular smooth muscle to mechanical stretch, first observed in isolated segments of canine carotid artery by Bayliss [1], is often postulated to be a mechanism of myogenic control of blood flow. In most cell types, a transient increase in intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) has been observed when cells are exposed to mechanical stress, and this increase is considered to be attributable to Ca 2ϩ influx through mechanosensitive ion channels [2]. Furthermore, the contraction in response to mechanical stimulation such as stretch has been known to be rate-dependent in the rat portal vein [3], the rabbit basilar artery [4], and the hamster cheek pouch arterioles [5]. Our previous studies indicated that the basilar arteries isolated from rabbit [4] and dog [6] treated with potassium channel blocker such as tetraethylammonium (TEA) easily produced contraction in response to a mechanical stimulation with varying rates of stretch. However, little information is available about the mechanotransduction mechanism, i.e., the signal transduction pathway that mediates conversion of mechanical stress to the specific cellular response including [Ca 2ϩ ] i mobilization and contraction. The cellular mechanisms underlying the effect of potassium blockers on the mechanotransduction also still remain unclear. Japanese Journal of Physiology, 51, 327-335, 2001 Key words: smooth muscle, basilar artery, mechanical stimulation, contraction, calcium.Abstract: Stretch evoked a contraction in a rate-dependent manner in canine basilar artery; slow stretch at rates less than 3 mm/s produced no active tension, whereas quick stretch at rates over 5 mm/s did. Large conductance Ca 2ϩ -activated K ϩ channel blockers, including charybdotoxin, iberiotoxin, and tetraethylammonium (TEA) sensitized the basilar artery to mechanical stimulation. TEA shifted the stretch rate-tension relationship toward the left. Thus, in the presence of TEA, the slow stretch (0.1-3 mm/s) could increase in intracellular Ca -insensitive component of quick stretch-induced contraction was eliminated by thapsigargin, but not by nicardipine. Ryanodine, cyclopiazonic acid, thapsigargin, U-73122, and calphostin C also abolished the nicardipineinsensitive component of quick stretch-induced contraction. These results suggest that the slow stretch-induced contraction was exclusively dependent on the Ca 2ϩ influx through L-type voltage-dependent Ca 2ϩ channels (VDCs), whereas the quick stretch-induced contraction was dependent on Ca 2ϩ release from sarcoplasmic reticulum (SR) and Ca 2ϩ influx through L-type VDCs.

The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels

“…On the other hand, the myogenic contractions were evident in cerebral arteries (Toda et al, 1978;Nakayama, 1982). Cerebroarterial smooth muscle contracted in response to stretch; this contraction seems to be mediated by an increased influx of Ca 2ϩ (Kimura et al, 2000;Obara et al, 2001). It is suggested that herbimycin-sensitive protein tyrosine kinase activity is involved in Ca 2ϩ influx through L-type channels (Matsumoto et al, 1997;Kimura et al, 2000).…”

Interactive Role of Protein Phosphatase 2A and Protein Kinase Cα in the Stretch-Induced Triphosphorylation of Myosin Light Chain in Canine Cerebral Artery

“…The experimental method for stretching ring segments of the canine cerebral artery has previously been described in detail [7]. Briefly, the endothelium was eliminated by gentle rubbing of the intimal layer of the artery with a moist cotton pledget.…”

“…Isotonic 80 m M KCl-Tyrode’s solution was prepared by replacement of NaCl with an equimolar amount of KCl. We previously reported that a slow stretch at a rate of 1 mm/s from L i to 1.5 L i elicited a reproducible contraction when the artery was treated with TEA (5 m M ) or iberiotoxin (100 n M ) [7]. The slow stretch-induced contraction reached a maximum at almost 1 min after stretching and then gradually decreased to near basal level within 15 min.…”

“…This myogenic response contributes to the autoregulation of blood flow, and is also considered to be one of the primary mechanisms responsible for basal vascular tone [1,2,3,4,5]. We previously reported that the cerebral artery of various animal species including dogs [6,7,8], rabbits [2, 9] and rats [10, 11] was particularly sensitive to mechanical stretching and pressure, leading to a contraction. We found that slow stretching produces contraction only when the large conductance Ca 2+ -activated K + channels (BK channels) of the artery are inhibited by iberiotoxin and tetraethylammonium (TEA) [7] or by 20-hydroxyeicosatetraenoic acid (20-HETE) [12], an endogenous cytochrome P450 metabolite of arachidonic acid.…”

“…We previously reported that the cerebral artery of various animal species including dogs [6,7,8], rabbits [2, 9] and rats [10, 11] was particularly sensitive to mechanical stretching and pressure, leading to a contraction. We found that slow stretching produces contraction only when the large conductance Ca 2+ -activated K + channels (BK channels) of the artery are inhibited by iberiotoxin and tetraethylammonium (TEA) [7] or by 20-hydroxyeicosatetraenoic acid (20-HETE) [12], an endogenous cytochrome P450 metabolite of arachidonic acid. More recently, it has been reported that the inhibition of BK channels under pathophysiological conditions, such as intracellular acidosis [13] and type 1 diabetes [14], results in increased vasoconstriction of cerebral artery.…”