title: Calcium-contraction relationship in rat mesenteric arterial smooth muscle. Effects of exogenous and neurogenic noradrenaline.
abstract: We evaluated the relationship between intracellular calcium concentration ([Ca2+]i) and vasoconstriction during the presence of exogenous noradrenaline (NA) and sympathetic nerve stimulation. An imaging technique was used to determine calcium/tension relationships in isolated rat mesenteric resistance arteries that had been mounted for recording of isometric tension development and loaded with Fura-2/AM. Experiments were performed after depletion of vasodilator neuropeptides and in the continuous presence of 1 microM propranolol, 3 microM indomethacin, and 30 microM nitro-l-arginine. NA (10 microM) was shown first to induce a further increase in tension, but not [Ca2+]i, during the contraction induced by 125 mM K+. Subsequently, calcium/tension relationships were determined during stimulation with graded increases in extracellular [K+] (5. 9-125 mM K+), cumulative administration of NA (0.2-10 microM) and electrical field stimulation of perivascular nerves (EFS, 1-16 Hz). A basal calcium/tension relationship without the calcium-sensitizing property of NA was constructed using a cumulative concentration/response curve of 5.9-125 mM K+ in arteries after prior exposure to the irreversible alpha-adrenoceptor antagonist phenoxybenzamine (POB). K+ series before and during alpha-blockade were also studied using the combination of the alpha1-antagonist prazosin and alpha2-antagonist yohimbine yielding comparable results as with POB. Calcium/tension curves obtained in the presence of NA, K+ and during EFS all were shifted to the left compared with the basal condition and all showed a similar slope indicating that neurogenically released NA is equally capable of inducing calcium sensitization in smooth muscle of mesenteric resistance arteries as exogenously applied NA. In the presence of exogenous and endogenous NA we not only observed an elevated contractile response for a given increase in [Ca2+]i, but also an attenuated rise in [Ca2+]i for a given intensity of stimulation. This suggests that the agonist-induced calcium-sensitization is accompanied by a reduction of the rise in [Ca2+]i.
authors.affiliation: Department of Pharmacology, Cardiovascular Research Institute Maastricht, Universiteit Maastricht, Maastricht, P.O. Box 616, NL-6200 MD Maastricht, The Netherlands.
authors.forename: N J
authors.initials: NJ
authors.lastname: Raat
authors.forename: G E
authors.initials: GE
authors.lastname: Wetzels
authors.forename: J G
authors.initials: JG
authors.lastname: De Mey
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D016257:Fura-2; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D005456:Fluorescent Dyes; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine; D011224:Prazosin