Increase In Contractile Tension Research Articles

Spatiotemporally Controlled Myosin Relocalization and Internal Pressure Generate Sibling Cell Size Asymmetry

SummaryMetazoan cells can generate unequal-sized sibling cells during cell division. This form of asymmetric cell division depends on spindle geometry and Myosin distribution, but the underlying mechanics are unclear. Here, we use atomic force microscopy and live cell imaging to elucidate the biophysical forces involved in the establishment of physical asymmetry in Drosophila neural stem cells. We show that initial apical cortical expansion is driven by hydrostatic pressure, peaking shortly after anaphase onset, and enabled by a relief of actomyosin contractile tension on the apical cell cortex. An increase in contractile tension at the cleavage furrow combined with the relocalization of basally located Myosin initiates basal and sustains apical extension. We propose that spatiotemporally controlled actomyosin contractile tension and hydrostatic pressure enable biased cortical expansion to generate sibling cell size asymmetry. However, dynamic cleavage furrow repositioning can compensate for the lack of biased expansion to establish physical asymmetry.

Spatiotemporally Controlled Myosin Relocalization and Internal Pressure Cause Biased Cortical Extension to Generate Sibling Cell Size Asymmetry

Metazoan cells can generate unequal sized sibling cells during cell division. This form of asymmetric cell division depends on spindle geometry and Myosin distribution but the underlying mechanics are unclear. Here, we use atomic force microscopy and live cell imaging to elucidate the biophysical forces involved in the establishment of physical asymmetry in Drosophila neural stem cells. We show that the force driving initial apical cortical expansion is provided by hydrostatic pressure, peaking shortly after anaphase onset, and enabled by a relieve of actomyosin contractile tension on the apical cell cortex. The subsequent increase in contractile tension at the cleavage furrow, combined with the relocalization of basally located Myosin results in basal membrane extension and sustained apical expansion. We propose that spatiotemporally controlled actomyosin contractile tension and hydrostatic pressure enables biased cortical expansion to generate sibling cell size asymmetry.

Vasoconstrictor and Inotropic Effects Induced by the Root Bark Extracts of Anthocleista schweinfurthii

The present study was undertaken to investigate the cardiovascular effect of three extracts from the root bark of Anthocleista schweinfurthii Gilg.: an aqueous extract (AE), a dichloromethane extract (DCMR) and a fraction enriched in cardiac glycoside type compounds (CARDAN). In isolated perfused frog heart, bolus injection of the extracts produced a positive inotropic effect. The responses to AE and DCMR, but not to CARDAN, were depressed by propranolol. In isolated rat aorta, DCMR produced a transient increase in contractile tension while AE and CARDAN induced a sustained constriction. AE vasoconstrictor effect was abolished by phentolamine, while contraction evoked by CARDAN was antagonized by verapamil. In aortic rings contracted in low K+ media, the addition of K+ evoked a relaxation, which was abolished by ouabain, depressed by DCMR but not affected by either A(E) or CARDAN. These observations indicate that Anthocleista schweinfurthii contains substances that promote vasoconstriction and increase cardiac contraction. The effect of DCMR was only partially mediated by inhibition of the Na+ pump while the mechanism of action of A(E) and CARDAN was distinct from the inhibition of the Na+, K+ - ATPase pump, but could involve adrenergic receptors, or either direct or indirect activation of L-type calcium channels.

Effects of nicotine on rat sternohyoid muscle contractile properties

Obstructive sleep apnoea (OSA) is a major clinical disorder characterised by recurring episodes of pharyngeal collapse during sleep. At present, there remains no satisfactory treatment for OSA. Pharmacological therapies as a potential treatment for the disorder are an attractive option and include agents that increase the contractility of the pharyngeal muscles. The aim of the present study was to examine the effects of nicotine on upper airway muscle contractile properties. In vitro isometric contractile properties were determined using strips of rat sternohyoid muscle in physiological salt solution containing nicotine (0-100 microg/ml) at 25 degrees C. Isometric twitch and tetanic tension, contraction time, half-relaxation time and tension-frequency relationship were determined by electrical field stimulation with platinum electrodes. Fatigue was induced by stimulation at 40 Hz with 300 ms trains at a frequency of 0.5 Hz for 5 min. Nicotine at a concentration of 1 microg/ml was associated with a significant increase in sternohyoid muscle specific tension compared to control data. Dose-dependent increases in contractile tension were not observed. Nicotine had effects on tension-frequency relationship and endurance properties of the sternohyoid muscle at some but not all doses. A leftward shift in the tension-frequency relationship was observed at low stimulus frequencies (20-30 Hz) for nicotine at a concentration of 1 and 5 microg/ml and a significant increase in fatigue resistance was observed with nicotine at a concentration of 10 microg/ml. As fatigue of the upper airway muscles has been implicated in obstructive airway conditions, a pharmacological agent that improves muscle endurance may prove useful as a potential treatment for such disorders. Therefore, further studies of the effects of nicotinic agonists on upper airway function are warranted.

Are Prostanoids Related to Positive Inotropism by UTP and ATP?

Uridine 5′-triphosphate (UTP) and adenosine 5′-triphosphate (ATP) induce biphasic inotropic effects: first a decrease and then an increase in contractile tension were observed in isolated rat myocardial tissues. Inotropic effects were higher in atrial tissue than in ventricular or papillary muscle; thus, experiments were mostly carried out on rat atria. In this research, we mainly studied positive inotropism by using selective inhibitors of the arachidonic acid cascade. The natural compounds luffariellolide and aristolochic acid, two inhibitors of PLA₂, both inhibited positive inotropism by UTP but not by ATP, whereas they did not modify their negative inotropism. Indomethacin (5 µmol/l), an inhibitor of COX-1, reduced positive inotropism by UTP but not by ATP, without modifying their negative inotropism. Nimesulide (1 µmol/l), an inhibitor of COX-2, did not change any of the effects caused by nucleotides. Nor did NDGA (10 µmol/l), an inhibitor of lipoxygenase, change inotropism by nucleotides. Arachidonic acid pretreatment (10 µmol/l) increased inotropic effects by UTP without affecting those of ATP. These data suggest that there are differences in the mechanisms responsible for the positive inotropism caused by UTP in comparison with ATP; the effect of UTP depends on PLA₂ activation and PG_s release, whereas that of ATP does not.

Do ATP and UTP involve cGMP in positive inotropism on rat atria?

ATP and UTP induced a dual inotropic effect in rat left atria: first a decrease and then an increase in contractile tension were observed. PPADS, an antagonist of P2X receptors, inhibited positive inotropism induced by ATP and α,β-meATP. Chiefly, we investigated intracellular mechanisms responsible for the positive inotropism. We tested cromakalim and glibenclamide, an activator and an inhibitor, respectively, of ATP-sensitive K + channels. These compounds did not influence the effects of ATP. IBMX, a phosphodiesterase inhibitor, and H-7, an inhibitor of protein kinase C and cAMP-dependent protein kinase, did not modify the inotropic effects of ATP. Instead, H-8, an inhibitor of cAMP- and cGMP-dependent protein kinases, strongly inhibited the positive effects of both ATP and UTP, suggesting the possible involvement of cGMP in the inotropism. Also, LY 83583, an inhibitor of cGMP production, reduced positive inotropism by α,β-meATP, ATP and UTP. Moreover, 8-Br-cGMP (50 μM), a stable analogue of cGMP, inhibited positive inotropism by all nucleotides. Lastly, we determined intracellular cGMP levels by RIA; the cyclic nucleotide increased during positive inotropism induced by ATP and UTP. The results regarding positive inotropism suggest that: (a) ATP acts through P2X receptors, while UTP may act by P2X, but also through PPADS-insensitive receptors; and (b) changes in intracellular cGMP concentration are involved in this inotropic effect.

Change in Ca2+ sensitivity of cerebrovascular smooth muscle in experimental chronic cerebral vasospasm.

The mechanism of chronic cerebral vasospasm was investigated by examining the relation between cytosolic Ca2+ level ([Ca2+]i) and muscle contraction in vascular smooth muscle after experimental vasospasm produced by the two-hemorrhage method in the canine basilar artery. [Ca2+]i and tension were recorded simultaneously with a fluorimeter using the arterial strips with a Ca2+ indicator, fura-2. High K+ concentration (72.4 mM) and U-46619 (thromboxane A2 analogue, 10(-8) M) were used as stimulants. The increase in contractile tension per [Ca2+]i per unit cross-sectional area was calculated, and compared for the vasospasm and the control groups. The increase in [Ca2+]i in the vasospasm group was smaller than that in the control group, so the increase in tension per [Ca2+]i per unit sectional area was larger in the vasospasm group. This value was much larger for the contraction induced by U-46619 than that induced by high K+ concentration in both groups. These results suggest that there is an increase in the basal Ca2+ sensitivity of the contractile elements in vasospastic vessels. In addition, the U-46619-induced increase in Ca2+ sensitivity seemed to be augmented in the vasospasm group.

Hypothermia Enhances Contractility in Cerebral Arteries of Newborn Lambs

Hypothermia is the major factor influencing autoregulatory properties of the cerebral circulation in human infants undergoing hypothermic cardiopulmonary bypass. The present investigation evaluated the effect of decreased temperature on the contractility of isolated middle cerebral arteries obtained from newborn lambs. Reducing bath temperature from 37 to 21°C caused a temperature-dependent increase in contractile tension, achieving 1.32 ± 0.09 g above resting tension (0.75 g). Pretreatment with nonselective (α1 and α2) α-adrenoceptor antagonist, phentolamine (10-5 M), with an inhibitor of nitric oxide synthase, NG-nitro-l-arginine methyl ester hydrochloride (10-4 M), and with a cyclooxygenase inhibitor, indometbacin (10-5 M), did not affect the contractile response to a decrease in bath temperature from 37 to 21°C. Furthermore, cerebral arteries were responsive to both norepinephrine (constriction) and sodium nitroprusside (relaxation) and the sensitivity of cerebral arteries to the sympathetic neurotransmitter norepinephrine appears to be enhanced at low temperatures. We postulate that direct cerebral vasoconstriction and enhanced adrenergic contractility may be responsible for increased cerebrovascular resistance during and after hypothermic cardiopulmonary bypass with possible ischemic cerebral injury and neurological sequelae.

Dual effect of ATP and UTP on rat atria: which types of receptors are involved?

The effects of adenine compounds and UTP were examined in electrically driven rat left atria. ATP, ADP, AMP, adenosine and UTP caused a dual inotropic effect: first a rapid decrease in contractility, and second an increase in contractile tension. alpha,beta-Methylene ATP caused an increase in contractile tension only, whereas 2-methylthio-ATP only induced a negative inotropic effect, 1,3-Dipropyl-8-cyclopentylxanthine inhibited the negative effects of ATP and adenosine, whereas 3,7-dimethyl-1-propargylxanthine did not influence the effects of ATP. Suramin but not reactive blue 2 antagonized the positive inotropism induced by ATP and alpha,beta-methylene ATP. Suramin also abolished the positive inotropic effect induced by UTP. These results demonstrate that ATP may induce negative inotropism directly by an action on A1-adenosine receptors and positive inotropism by an action on P2x-purinoceptors. UTP induces a positive inotropic effect mediated by suramin-sensitive receptors.

Positive inotropic effects of CGRP and isoprenaline: Analogies and differences

In guinea-pig isolated left atria, electrically stimulated at 1 Hz, isoprenaline and calcitonin gene-related peptide (CGRP) induced a positive inotropic effect in the same concentration range (0.3–100 nM). The increase in contractile tension induced by both agonists was associated with a reduction in time to peak tension and relaxation time. However CGRP was more active than isoprenaline in reducing the time to peak; this effect was more evident when the bath temperature was reduced from 30° to 24°C. The positive inotropic effects of isoprenaline and CGRP were potentiated by forskolin (30 nM), a direct activator of adenylcyclase; on the other hand, cholera toxin (1 μg/ml), which irreversibly ribosylates Gs protein, did not modify the effect of CGRP, while antagonizing the concentration-response curve for isoprenaline. It is concluded that the increase in atrial contractile tension produced by isoprenaline and CGRP are linked to the adenylcyclase system in a different manner.

Clenbuterol, a beta 2-receptor agonist, reduces net bone loss in denervated hindlimbs

Clenbuterol treatment for several weeks prevented up to one-third of the reduction in mineralization of femurs and tibias caused by sectioning of the sciatic nerve in young rats. The normalizing effect of clenbuterol on bone mineral content was directly proportional to similar alterations in muscle mass, which in turn could be abolished by ablation of the triceps surae or hindlimb unweighting and reduced by hypophysectomy. In contrast to the effects of inactivity, ovariectomy caused small reductions (2-4%) in bone density that were not affected by clenbuterol and were not accompanied by changes in ash weight. Together, our results suggest that the ability of beta 2-agonists to retard the loss in net muscle mass and enhance contractile tension can oppose net bone loss caused by denervation. Increases in contractile tension caused by beta 2-agonists may enhance the utility of exercise or electrical stimulation as countermeasures for the effects of scoliosis, prolonged bed rest, spinal cord injury, or weightlessness in space on bone mass.

Modulation of vascular reactivity to serotonin in the dog lung

Experiments were conducted to compare the effects of cyclooxygenase inhibition (COI) on vascular reactivity to serotonin (5-HT) in the isolated blood-perfused canine left lower lung lobe (LLL) and in isolated canine intrapulmonary lobar artery rings with and without a functional endothelium. LLLs (n = 6), perfused at constant blood flow, were challenged with bolus doses of 50, 100, and 250 micrograms 5-HT before COI, after COI with 45 microM meclofenamate, and after infusion of prostacyclin (PGI2) during COI. Lobar vascular resistance was segmentally partitioned by venous occlusion. Pulmonary arterial pressure increased from 13.5 +/- 1.0 to 16.3 +/- 0.8 cmH2O (P less than 0.01) after COI but declined to 13.1 +/- 1.1 cmH2O (P less than 0.01) subsequent to PGI2 infusion (91.3 +/- 14.5 ng.min-1.g LLL-1). The pulmonary arterial pressure changes were related to changes in postcapillary resistance. The dose-dependent pressor response to 5-HT was potentiated by COI (P less than 0.01) but reversibly attenuated (P less than 0.05) by PGI2 infusion. Isolated intrapulmonary artery rings (2-4 mm diam) exhibited a dose-related increase in contractile tension to 5-HT. The response to 5-HT was enhanced (P less than 0.05) in rings devoid of a functional endothelium. However, COI (10 microM indomethacin) did not alter (P greater than 0.05) the dose-related increase in contractile tension to 5-HT in rings with an intact endothelium. Our results suggest that both PGI2 and endothelium-derived relaxing factors modulate pulmonary vascular reactivity to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

Novel cellular activities for low density lipoprotein in vascular smooth muscle cells.

Hyperlipidemia and hypertension play important roles in the pathogenesis of atherosclerosis. To investigate the underlying intracellular mechanisms, we studied the effect of various concentrations of low density lipoprotein from normolipidemic subjects on concentrations of free intracellular calcium, intracellular pH, DNA synthesis, and vascular tone in vascular smooth muscle cells and rings from rat aortas. Low density lipoprotein in the range of 1-15 micrograms/ml induced a dose-dependent increase of concentration of free intracellular calcium and a biphasic change of the intracellular pH. Similar concentrations of low density lipoprotein led to an enhanced DNA synthesis. Furthermore, cumulative addition of 1-15 micrograms/ml low density lipoprotein produced a dose-dependent increase in contractile tension of thoracic aortic rings from rats. The maximal low density lipoprotein-induced contractile response was approximately 70% of that induced by 40 mM KCl. These findings indicate that low concentrations of low density lipoprotein occurring, for example, in the extravascular fluid might contribute to the pathogenesis of cardiovascular diseases by enhancing cell proliferation and vasoconstriction by changing intracellular calcium and intracellular pH.

Vasoconstriction: A novel activity for low density lipoprotein

Low density lipoprotein plays an important role in the pathogenesis of atherosclerosis. Cumulative addition of 1–30 μg/ml of LDL from normolipidemic subjects produced a dose-dependent increase in contractile tension of thoracic aortic rings from rats. The maximal LDL-induced contractile response was approximately 30 % of that induced by 1 μM norepinephrine. Similar concentrations of LDL induced a dose-dependent transient increase of the concentration of intracellular free calcium, and a biphasic change of the intracellular PH in cultured rat vascular smooth muscle cells. We conclude that low density lipoprotein occuring for example in the extravascular fluid can mediate vasoconstriction by changes in cytosolic calcium and intracellular pH.

Calcitonin gene-related peptide increases cAMP, tension, and rate in rat atria

Calcitonin gene-related peptide (CGRP) was studied in rat isolated atria to ascertain the role of cyclic nucleotides in the positive chronotropic and inotropic actions of this novel cardiac neuropeptide. In electrically driven left and right atria, CGRP (3-100 nM) caused concentration-dependent increases in contractile tension that developed slowly and persisted for greater than 30 min while CGRP remained in the bath. In spontaneously beating right atria, CGRP (3-100 nM) caused concentration-dependent prolonged increases in heart rate and small transient increases in contractile force. CGRP (100 nM, 2 min) elevated adenosine 3',5'-cyclic monophosphate (cAMP) content in left atria 2-fold and right atria 1.6-fold. Time courses and concentration-response relationships for cAMP elevation correlated well with chronotropic and inotropic responses. Guanosine 3',5'-cyclic monophosphate (cGMP) levels in both atria were not altered by CGRP. Compared with norepinephrine (NE), CGRP was 14-fold more potent at increasing rate [50% effective concentration (EC50) = 4.55 +/- 0.48 nM for CGRP and 64.8 +/- 10.5 nM for NE] and 60-fold more potent at increasing contractile force (EC50 = 3.31 +/- 0.57 nM for CGRP and 201 +/- 18 nM for NE). Preincubation with atenolol (3 microM) or indomethacin (3 microM) did not alter chronotropic, inotropic, and cAMP responses to CGRP in atria, indicating that these responses were not mediated by released catecholamines or prostaglandins. The data are consistent with the hypothesis that CGRP causes positive chronotropic and isotropic effects via activation of cAMP responses in rat atrial myocardium.

Endothelin action on vascular smooth muscle involves inositol trisphosphate and calcium mobilization

Cultured endothelial cells release a potent vasoconstrictor peptide, endothelin. Cumulative addition of synthetic endothelin to isolated rabbit aortic rings elicited a concentration-dependent increase in contractile tension which was endothelium-independent. In cultured rabbit vascular smooth muscle cells loaded with the fluorescent dye fura 2, endothelin induced a concentration-dependent increase in [Ca2+]i over the range of 0.01 to 100 nM. Moreover, in the absence of extracellular Ca2+, endothelin could still induce an increase in [Ca2+]i. In addition, endothelin stimulated 45Ca2+ efflux from preloaded vascular smooth muscle cells in the presence and absence of extracellular Ca2+, as well as stimulating 45Ca2+ influx in a concentration-dependent manner. Measurement of inositol phosphates in [3H]-myoinositol-labelled vascular vascular trisphosphate. Unlabelled endothelin inhibited (125I)-endothelin binding to cultured rabbit vascular smooth muscle cells in a concentration-dependent manner. Binding was not inhibited by other vasoactive hormones or calcium channel ligands, suggesting cell surface receptors specific for endothelin. We conclude that one of the initial membrane events in the action of endothelin is to induce phospholipase C-stimulated PIP2 hydrolysis and that this signalling mechanism is initiated by endothelin/receptor interaction at the plasma membrane.

Antagonism between (–)‐N6‐phenylisopropyl‐adenosine and the calcium channel facilitator Bay K 8644, on guinea‐pig isolated atria

Antagonism between (-)-N6-phenylisopropyladenosine (PIA) and the dihydropyridine calcium channel facilitator Bay K 8644 was investigated in guinea-pig spontaneously beating or electrically driven isolated atria, taken from normal and from reserpine-treated animals. PIA (3-100 nM) produced a dose-dependent decrease in contractile tension and frequency in spontaneously beating atria being more effective in reserpinized preparations. Bay K 8644 (5-200 nM) produced an increase in contractile tension in both normal and reserpinized atria. In electrically driven left atria the positive inotropic effect of Bay K 8644 was similar to that in spontaneously beating preparations. The positive chronotropic effect of Bay K 8644 was slight and variable. PIA produced a rightward parallel shift of the concentration-response curves for the positive inotropic effects of Bay K 8644 in all experimental conditions. In spontaneously beating atria from normal guinea-pigs, the Schild regression plot was linear and its slope near to unity; pA2 of PIA 8.63 +/- 0.05 (IC50 2.35 +/- 0.25 nM). In electrically driven atria the antagonism by PIA of the effects of Bay K 8644 was apparently competitive, and the IC50 of PIA was 18.6 +/- 0.4 nM. PIA antagonized the positive chronotropic effect of Bay K 8644 in spontaneously beating preparations, both from normal and from reserpine-treated animals. Carbachol did not modify the positive inotropic effects of Bay K 8644. These data indicate that PIA may interact with Bay K 8644 at the level of the slow calcium channels, and may decrease the transmembrane calcium flux into the cell.

Positive inotropic effect of a stable analogue of PGI 2 and of PGI 2 on isolated guinea pig atria. Mechanism of action

Fluoroprostacyclin (10,10-difluoro-13,14-dehydroprostacyclin) a stable analogue of PGI2, induced an increase of contractile tension and a positive chronotropic effect on spontaneously beating guinea-pig atria. The increase in contractile tension was proportional to the dose (10(-8) to 2.5 X 10(-7) M) and never exceeded 40% of absolute initial controls. The chronotropic positive effect was low (12 +/- 4%) and not dose-dependent. The positive inotropic effect was also evident on electrically driven atria and was greater at the slower rates of stimulation. Atria from guinea pigs pretreated with reserpine were still sensitive to fluoroprostacyclin, although to a lower degree. The use of appropriate agonists and antagonists excluded the possibility that beta and alpha receptors are involved in the positive inotropic effect of fluoroprostacyclin. PGI2 showed the same behavior as fluoro-PGI2. Prostacyclins were able to reverse the decrease of contractility induced by verapamil, nifedipine, tetrodotoxin and xylocaine. But the reversal by PGI2 was no longer evident when the atrial contractility was completely abolished by the presence of these drugs in high concentrations. The inotropic effect of prostacyclins was more evident when Ca2+ was reduced in the medium. These results demonstrate that the cardiostimulant effect of prostacyclins is not simply adrenergic in origin. A direct effect on ion movements, mainly dependent on Ca2+ transmembranes fluxes, may be largely responsible for their positive inotropic effect.

Alpha-Sympathomimetic amines and calcium-mediated action potentials in guinea-pig ventricular muscle.

1 The ability of amines, having alpha- or alpha- and beta-adrenoceptor stimulating activity, to restore excitability and contractility in heart preparations partially depolarized by potassium, was investigated in guinea-pig ventricular muscle in order to elucidate the mechanism of the positive inotropic effect mediated via alpha-adrenoceptors. 2 In preparations in which fast sodium channels were inactivated by K+-rich medium (22 mM) slow electrical responses as well as contractions were consistently induced by high concentrations of phenylephrine (10(-4) to 3 X 10(-4) M) and synephrine (3 X 10(-4) M). 3 The restorative effective effects of both phenylephrine and synephrine were unaffected by phentolamine (10(-5) M) but were readily abolished by practolol (10(-5) M) or sotalol (10(-5) M). 4 Methoxamine induced a dose-dependent positive inotropic effect in ventricular strips paced at 0.5 Hz in normal Tyrode solution; the maximum increase in contractile tension was obtained with methoxamine 10(-4) M. However, at the same concentration, the amine did not induce slow electrical responses in potassium-depolarized preparations. 5 It is concluded that the induction of slow responses by phenylephrine and synephrine is due to beta-adrenoceptor stimulation, and that the increase in cardiac contractility caused by alpha-adrenoceptor stimulation does not involve an increase in slow inward calcium current.

Prostacyclin-induced contraction of isolated aortic strips from normal and spontaneously hypertensive rats (SHR)

Prostacyclin (PGl 2) (500-5,000 ng/ml) produced a concentration-dependent increase in contractile tension of isolated thoracic aortic strips (AS) from normotensive (WKY) and spontaneously hypertensive rats (SHR). No significant differences were noted between this response to PGl 2 in these two groups. Lower concentrations of PGl 2 (10 pg/ml — 100 ng/ml) caused neither contraction nor relaxation of agonist-contracted tissue. PGl 2 (500-5,000 ng/ml) did not relax KCl or methoxamine contracted AS. In concentrations above 100 ng/ml, PGl 2 caused a further increase in tension in KCl-depolarized preparations. The constrictor effect of PGl 2 on AS was attenuated by verapamil pretreatment or removal of extracellular Ca ++ from the physiological buffer. This inhibitory effect of Ca ++ deficiency on the PGl 2 response was significantly greater in AS from SHR compared to WKY tissue. The stable metabolite of PGl 2, 6-keto PGF 1a, caused a weak constrictor effect (40% of KCl reference contraction) over the concentration range 1,000–5,000 ng/ml. Contraction induced by PGl 2 was not prevented by pretreatment with antagonists of adrenergic, histamine, serotonin or cholinergic receptors. The contraction response of the rat AS to PGl 2 is similar to that reported for porcine coronary artery and rabbit aortic tissues in vitro.