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Biomedical subjects

T Akata

Publications and source records attributed to T Akata.

35 records · Page 2Linked to original sources
PubMed1997

Hemidiaphragmatic paralysis following subclavian vein catheterization.

The right subclavian artery was inadvertently punctured during attempted preoperative insertion of a right subclavian venous catheter in a 59-yr-old woman undergoing radical hysterectomy. Large supraclavicular swelling became apparent soon after the arterial puncture. The postoperative chest X-ray obtained approximately 24 h after the catheterization revealed significant elevation of the right hemidiaphragm, which was further augmented on the 2nd to 4th postoperative days; oxygenation was concurrently impaired during these days. It was clinically judged that the hemidiaphragmatic paralysis was responsible for the elevated diaphragm. Both chest roentogenogram and arterial blood gas analyses started to improve on the 5th day, finally returning to normal on the 6th day. It is unlikely that the surgical procedure caused the paralysis, because it dealt only with the lower abdomen. Rather, the attempts at the subclavian venous catheterization probably caused the phrenic nerve paralysis, because the phrenic nerve travels very close to the subclavian vessels. Both the large haematoma formation following the arterial puncture and the time course of the paralysis suggest that compression of the right phrenic nerve by the haematoma, rather than needle trauma, was responsible for the paralysis.

Catheterization, Central Venous↗
PubMed1997

Is guanosine-5'-triphosphate involved in calcium-activation of contractile proteins in vascular smooth muscle?

Isometric tension was measured to investigate the effects of guanosine-5'-triphosphate (GTP) on the run-down of myofilament Ca2+ sensitivity in isolated rat mesenteric arteries permeabilized with beta-escin. The Ca2+ sensitivity assessed by the EC50 value for the Ca2+ (0.1-100 microM)-tension relationship progressively runs down in the control strips, while it was well-preserved for 5-successive Ca2+ applications in the presence of GTP (50 microM); no significant difference was found in the Ca2+ sensitivity observed with the 1st Ca2+ application between the control and GTP-treated strips. Guanosine-5'-(2-O-thio) diphosphate (GDP beta S, 100 microM) significantly decreased the Ca2+ sensitivity with the 1st Ca2+ application and eliminated the run-down of Ca2+ sensitivity. GTP (3-150 microM), applied to the strips submaximally precontracted with Ca2+, had a little effect on the Ca2+ contractions in the early stage of experiments, but dramatically enhanced the Ca2+ contractions in their later stage; its latter effect was mimicked by guanosine-5'-(3-O-thio) triphosphate (GTP gamma S) and reversed by GDP beta S (100 microM). The results suggest: 1) loss of endogenous GTP following permeabilization is involved in the run-down of Ca2+ sensitivity; and 2) activation of G-proteins is involved in Ca(2+)-activation of contractile proteins.

Animals↗
PubMed1996

Dual actions of halothane on intracellular calcium stores of vascular smooth muscle.

BACKGROUND: Halothane has been reported to affect the integrity of intracellular Ca2+ stores in a number of tissues including vascular smooth muscle. However, the actions of halothane on intracellular Ca2+ stores are not yet fully understood. METHODS: Employing the isometric tension recording method, the action of halothane in isolated endothelium-denuded rat mesenteric arteries under either intact or beta-escinmembrane-permeabilized conditions was investigated. RESULTS: Halothane (0.125-5%) produced concentration-dependent contractions in Ca2+ free solution in both intact and membrane-permeabilized muscle strips. Ryanodine treatment or repetitive application of phenylephrine eliminated both caffeine-and halothane-induced contractions in the Ca2+ free solution. When either halothane and caffeine, caffeine and halothane, phenylephrine and halothane, or inositol 1,4,5-triphosphate and halothane were applied consecutively in the Ca2+ free solution in either intact or membrane-permeabilized muscle strips, the contraction induced by application of the second agent of the pair was inhibited compared to application of that agent alone. However, when procaine was applied before and during application of the first agent, the contraction induced by the first agent was inhibited and the contraction induced by the second agent was restored. Heparin inhibited the inositol 1,4,5-triphosphate-mediated contraction, but not contractions induced by halothane or caffeine. Halothane (0.125-5%), applied during Ca2+ loading, produced concentration-dependent inhibition of the caffeine contraction (used to estimate the amount of Ca2+ in the store) in both intact and membrane-permeabilized muscle strips. In contrast, halothane applied with procaine during Ca2+ loading produced concentration-dependent enhancement of the caffeine contraction. This enhancement was observed only in the intact but not in the membrane-permeabilized condition. CONCLUSIONS: Halothane has two distinct actions on the intracellular Ca2+ stores of vascular smooth muscle, a Ca2+ releasing action and a stimulating action on Ca2+ uptake. Halothane releases Ca2+ from the stores that are sensitive to both caffeine/ryanodine and phenylephrine/inositol 1,4,5-triphosphate through a procaine-sensitive mechanism. The observed inhibitory effect on Ca2+ uptake is probably caused by the Ca2+ uptake after blockade of Ca2+ release may be membrane-mediated.

Anesthetics, Inhalation↗
PubMed1995

Volatile anaesthetic actions on norepinephrine-induced contraction of small splanchnic resistance arteries.

The aim of this study was to investigate volatile anaesthetic action on small splanchnic resistance arteries. Employing isometric tension recording, we studied the effects of clinically relevant concentrations (0.25-1.25 minimum alveolar concentration (MAC)) of isoflurane, sevoflurane and enflurane on contractions induced by norepinephrine (NE), a sympathetic neurotransmitter, in the rabbit small mesenteric artery. Rhythmic oscillations were observed in contractile responses to NE. Both isoflurane (> or = 0.25 MAC, 0.5% (approximately 0.11 mM)) and sevoflurane (> or = 0.75 MAC, 2.8% (approximately 0.38 mM)) inhibited the NE (10 microM)-induced contraction with concomitant inhibition of average amplitude of the oscillations. Only enflurane (> or = 0.25 MAC, 0.7% (approximately 0.20 mM)) generated vasoconstriction superimposed on the NE-induced contraction; however, the vasoconstriction was transient and was followed by vasorelaxation. Concurrently, enflurane (> or = 0.25 MAC) strongly inhibited the average amplitude of the oscillations; higher concentrations (> or = 1.0 MAC) of enflurane completely eliminated the oscillations. The frequency of the NE-induced oscillations was less affected by the anaesthetics. The observed vasodilator action of these anaesthetics in small resistance arteries may contribute to their hypotensive effects in vivo. The potent inhibition of the rhythmic oscillations also may play a role in volatile anaesthetic-induced alterations in cardiovascular homeostasis.

Analysis of Variance↗
PubMed1995

Effects of volatile anesthetics on acetylcholine-induced relaxation in the rabbit mesenteric resistance artery.

BACKGROUND: Vascular endothelium plays an important role in the regulation of vascular tone. Volatile anesthetics have been shown to attenuate endothelium-mediated relaxation in conductance arteries, such as aorta. However, significant differences in volatile anesthetic pharmacology between these large vessels and the small vessels that regulate systemic vascular resistance and blood flow have been documented, yet little is known about volatile anesthetic action on endothelial function in resistance arteries. Furthermore, endothelium-dependent relaxation mediated by factors other than endothelium-derived relaxing factor (EDRF) has recently been recognized, and there is no information available regarding volatile anesthetic action on non-EDRF-mediated endothelium-dependent relaxation. METHODS: Employing isometric tension recording and microelectrode methods, the authors first characterized the endothelium-dependent relaxing and hyperpolarizing actions of acetylcholine (ACh) in rabbit small mesenteric arteries, and tested the sensitivities of these actions to EDRF pathway inhibitors and K+ channel blockers. They then examined the effects of the volatile anesthetics isoflurane, enflurane, and sevoflurane on ACh-induced endothelium-dependent relaxation that was sensitive to EDRF inhibitors and that which was resistant to the EDRF inhibitors but sensitive to blockers of ACh-induced hyperpolarization. The effects of the volatile anesthetics on endothelium-independent sodium nitroprusside (SNP)-induced relaxation were also studied. RESULTS: Acetylcholine concentration-dependently caused both endothelium-dependent relaxation and hyperpolarization of vascular smooth muscle. The relaxation elicited by low concentrations of ACh (< or = 0.1 microM) was almost completely abolished by the EDRF inhibitors NG-nitro-L-arginine (LNNA), oxyhemoglobin (HbO2), and methylene blue (MB). The relaxation elicited by higher concentrations of ACh (> or = 0.3 microM) was only attenuated by the EDRF inhibitors. The remaining relaxation, as well as the ACh-induced hyperpolarization that was also resistant to EDRF inhibitors, were both specifically blocked by tetraethylammonium (TEA > or = 10 mM). Sodium nitroprusside, a NO donor, produced dose-dependent relaxation, but not hyperpolarization, in the endothelium-denuded (E[-]) strips, and the relaxation was inhibited by MB and HbO2, but not TEA (> or = 10 mM). One MAC isoflurane, enflurane, and sevoflurane inhibited both ACh relaxation that was sensitive to the EDRF inhibitors and the ACh relaxation resistant to the EDRF inhibitors and sensitive to TEA, but not SNP relaxation (in the E[-] strips). An additional finding was that the anesthetics all significantly inhibited norepinephrine (NE) contractions in the presence and absence of the endothelium or after exposure to the EDRF inhibitors. CONCLUSIONS: The results confirm that ACh has a hyperpolarizing action in rabbit small mesenteric resistance arteries that is independent of EDRF inhibitors but blocked by the K+ channel blocker TEA. The ACh relaxation in these resistance arteries thus appears to consist of distinct EDRF-mediated and hyperpolarization-mediated components. Isoflurane, enflurane, and sevoflurane inhibited both components of the ACh-induced relaxation in these small arteries, indicating a more global depression of endothelial function or ACh signaling in endothelial cells, rather than a specific effect on the EDRF pathway. All these anesthetics exerted vasodilating action in the presence of NE, the primary neurotransmitter of the sympathetic nervous system, which plays a major role in maintaining vasomotor tone in vivo. This strongly indicates that the vasodilating action of these anesthetics probably dominates over their inhibitory action on the EDRF pathway and, presumably, contributes to their known hypotensive effects in vivo. Finally, the vasodilating action of these anesthetics is, at least in part, independent from endothelium.

Acetylcholine↗
PubMed1995

Volatile anesthetic actions on contractile proteins in membrane-permeabilized small mesenteric arteries.

BACKGROUND: Volatile anesthetics have been shown to have vasodilating or vasoconstricting actions in vitro that may contribute to their cardiovascular effects in vivo. However, the precise mechanisms of these actions in vitro have not been fully elucidated. Moreover, there are no data regarding the mechanisms of volatile anesthetic action on small resistance arteries, which play a critical role in the regulation of blood pressure and blood flow. METHODS: With the use of isometric tension recording methods, volatile anesthetic actions were studied in intact and beta-escin-membrane-permeabilized smooth muscle strips from rat small mesenteric arteries. In experiments with intact muscle, the effects of-halothane (0.25-5.0%), isoflurane (0.25-5.0%), and enflurane (0.25-5.0%) were investigated on high K(+)-induced contractions at 22 degrees C and 35 degrees C. All experiments were performed on endothelium-denuded strips in the presence of 3 microM guanethidine and 0.3 microM tetrodotoxin to minimize the influence of nerve terminal activities. In experiments with membrane-permeabilized muscle, the effects of halothane (0.5-4.0%), isoflurane (0.5-4.0%), and enflurane (0.5-4.0%) on the half-maximal and maximal Ca(2+)-activated contractions were examined at 22 degrees C in the presence of 0.3 microM ionomycin to eliminate intracellular Ca2+ stores. RESULTS: In the high K(+)-stimulated intact muscle, all three anesthetics generated transient contractions, which were followed by sustained vasorelaxation. The IC50 values for this vasorelaxing action of halothane, isoflurane, and enflurane were 0.47 vol% (0.27 mM), 0.66 vol% (0.32 mM), and 0.53 vol% (0.27 mM), respectively, at 22 degrees C and were 3.36 vol% (0.99 mM), 3.07 vol% (0.69 mM), and 3.19 vol% (0.95 mM), respectively, at 35 degrees C. Ryanodine (10 microM) eliminated the anesthetic-induced contractions but had no significant effect on the anesthetic-induced vasorelaxation in the presence of high K+. In addition, no significant differences were observed in the dose dependence of the direct vasodilating action among these anesthetics with or without ryanodine at either the low or the high temperature. However, significant differences were observed in the vasoconstricting actions among the anesthetics, and the order of potency was halothane > enflurane > isoflurane. The Ca(2+)-tension relation in the membrane-permeabilized muscle yielded a half-maximal effective Ca2+ concentration (EC50) of 2.02 microM. Halothane modestly but significantly inhibited 3 microM (approximately the EC50) and 30 microM (maximal) Ca(2+)-induced contractions. Enflurane slightly but significantly inhibited 3 microM but not 30 microM Ca2+ contractions. Isoflurane did not significantly inhibit either 3 microM or 30 microM Ca2+ contractions. CONCLUSIONS: Halothane, isoflurane, and enflurane have both vasoconstricting and vasodilating actions on isolated small splanchnic resistance arteries. The direct vasoconstricting action appears to result from Ca2+ release from the ryanodine-sensitive intracellular Ca2+ store. The vasodilating action of isoflurane in the presence of high K+ appears to be attributable mainly to a decrease in intracellular Ca2+ concentration, possibly resulting from inhibition of voltage-gated Ca2+ channels. In contrast, the vasodilating actions of halothane and enflurane in the presence of high K+ appears to involve inhibition of Ca2+ activation of contractile proteins as well as a decrease in intracellular Ca2+ concentration in smooth muscle.

Animals↗
PubMed1995

Effects of heparin on the inhibitory action of protamine on endothelium-mediated vasorelaxation.

The precise mechanism(s) of inhibitory action of protamine on endothelium-mediated vasorelaxation has not been fully elucidated. In addition, no information is available regarding the effects of a heparin-protamine complex on the endothelium-mediated relaxation. Employing isometric tension recording methods, we studied the effects of heparin, an anionic substance, on the protamine-induced inhibition of acetylcholine (ACh)-induced vasorelaxation in isolated rabbit small mesenteric artery. Protamine (> or = 50 micrograms/ml) inhibited ACh (0.03-10 microM)-induced relaxation under a norepinephrine (10 microM)-stimulated condition (P < 0.05). The ACh relaxation, even 20 min after washout of protamine (150 micrograms/ml), was still significantly inhibited as compared to the control (before protamine) ACh relaxation, and further, it was not significantly different from the ACh relaxation maximally inhibited in the presence of protamine. Preapplication of heparin (700 U/ml) almost abolished the protamine inhibition (50 & 150 micrograms/ml) of the ACh relaxation. However, heparin (700 U/ml), applied on washout of protamine (150 micrograms/ml), had no effect on the prolonged protamine inhibition. In conclusion, a heparin-protamine complex had no direct effect on the endothelium-mediated relaxation, and the inhibitory action of protamine on the endothelium-mediated relaxation might be due to its polycationic property. The prolongation of protamine inhibition and the lack of effects of heparin on the prolonged protamine inhibition may suggest a toxic effect of protamine on the endothelium.

Acetylcholine↗
PubMed1995

Role of endothelium in oscillatory contractile responses to various receptor agonists in isolated small mesenteric and epicardial coronary arteries.

Employing the isometric tension recording method, we studied the role of endothelium or endothelium-derived relaxing factor (EDRF) in the generation of rhythmic oscillations observed in contractile responses to various receptor agonists in isolated rabbit small mesenteric and epicardial coronary arteries. Norepinephrine (NE, 0.1-10 microM) generated oscillatory contraction in endothelium-intact strips from the mesenteric arteries. Similarly, acetylcholine (ACh, 10 microM), histamine (10 microM) and serotonin (10 microM) generated oscillatory contraction in endothelium-intact strips from the coronary arteries. These agonist-induced oscillations in both arteries were consistently eliminated by either endothelial denudation or EDRF pathway inhibitors including NG-nitro L-arginine (30 and 100 microM), oxyhemoglobin (3 and 10 microM) and methylene blue (3 and 10 microM). In contrast, EDRF releasers such as ACh or A23187 augmented the oscillations in the endothelium-intact strips. SNP (0.03-30 microM) failed to generate oscillations in NE (10 microM)-preconstricted endothelium-denuded strips from the mesenteric arteries. In conclusion, these agonist-induced oscillations are probably mediated through EDRF. The inability of SNP to generate oscillations suggests the obligatory role of the endothelium in generation of the oscillations. The oscillatory release of EDRF by endothelial cells may be responsible for generation of the oscillations.

Acetylcholine↗
PubMed1993

Effects of heparin on the vasodilator action of protamine in the rabbit mesenteric artery.

1. The effects of protamine on the rabbit isolated small mesenteric artery were investigated both in the presence and in the absence of heparin, by the isometric tension-recording method. 2. The dissociation constant for the binding of heparin to protamine has never been previously reported, so in order to minimize the effects of protamine, known to have a vasodilator action, and to examine only the effects of a heparin-protamine complex, the experiments with heparin were performed in the presence of high concentrations of heparin (21-700 u ml-1), concentrations at which heparin itself does not affect the vascular tone. 3. Protamine (15-500 micrograms ml-1), in the absence of heparin, was found to inhibit (P < 0.05) noradrenaline (1 microM)-induced contractions both in endothelium-intact and in endothelium-denuded tissues. 4. Such vasodilator action of protamine in either endothelium-intact or -denuded tissues continued, even in the presence of excess heparin at a heparin/protamine (H/P) ratio of 1.4 u micrograms -1, but was almost completely blocked in the presence of a much greater excess of heparin (H/P ratio > or = 4.7 u micrograms -1): heparin was present both before and during the application of protamine. 5. The vasodilator action of protamine in the absence of heparin was prolonged both in the endothelium-intact and -denuded tissues after protamine had been washed out from the bath with Krebs solution. Although this washing out with a Krebs solution containing excess heparin (4.7 u ml-1) readily reversed such prolonged vasodilator action of protamine both in the endothelium-denuded strips and in the endothelium-intact strips which had been pretreated with inhibitors of the endothelium-derived relaxing factor (EDRF) pathway, it did not affect the prolonged vasodilator action of protamine in the endothelium-intact strips which received no pharmacological intervention.6. These results suggest that: (1) only protamine, not a heparin-protamine complex, exerts vasodilator action in vitro; (2) the vasodilator action of protamine presumably has an EDRF-mediated component;and (3) protamine probably exerts its direct vasodilator action without entering the smooth muscle cell.

Animals↗
PubMed1993

Heparin prevents the vasodilating actions of protamine on human small mesenteric arteries.

Despite the wide clinical use of protamine, the precise mechanisms of its hypotensive effects during reversal of heparin anticoagulation have not been elucidated fully. We, therefore, investigated the effects of protamine on isolated human small mesenteric arteries, both in the absence and presence of heparin, employing the isometric tension recording method. Protamine exerted vasodilating actions in the absence of heparin: 1) protamine (> or = 50 or 150 micrograms/mL) inhibited (P < 0.05) both norepinephrine (1 microM)- and high K+ (40 mM)-induced contractions in the presence of extracellular Ca2+ both in endothelium-intact and -denuded tissues; and 2) protamine inhibited (P < 0.05) norepinephrine (1 microM)-induced, but not caffeine (10 mM)-induced, contractions in the absence of extracellular Ca2+. Such vasodilating actions were blocked almost completely in the presence of heparin. We conclude that only protamine, but not a heparin-protamine complex, has a vasodilating action on the human arteries.

Aged↗
PubMed1992

Changes in end-tidal CO2 level following tourniquet deflation during orthopedic surgery.

We studied the changes in end-tidal CO(2) (ET(CO)(2)) and systemic responses after tourniquet deflation in spontaneously breathing and ventilation-controlled patients during orthopedic surgery of both the upper and/or the lower extremities. In most patients, increases in ET(CO)(2), heart rate, and Pa(CO)(2), as well as decreases in blood pressure and pH were observed. In every spontaneously breathing patient, the respiratory rate began to increase before the ET(CO)(2) reached a maximum. Arterial blood gas analysis suggested that the increase in ET(CO)(2) closely reflected the increase in Pa(CO)(2). Our study yielded new information on the ET(CO)(2) changes as follows: 1) the time for ET(CO)(2) level to reach a peak (peak time) was almost constant despite the considerable differences in the increases in ET(CO)(2) both in spontaneous breathing and ventilation-controlled groups and the peak time in the former group was shorter than that in the latter group; and 2) it was suggested that the increase in ET(CO)(2) in the spontaneously breathing patients was smaller than that in ventilation-controlled patients when both patients were subjected to the same conditions on tourniquet time and tourniqueted area. Our data showed that the increase in ET(CO)(2) (or Pa(CO)(2)) can be large and prolonged in some situations. Thus, we recommend continuous ET(CO)(2) monitoring and the proper hyperventilation at tourniquet deflation in order to minimize any adverse effects of acidosis.

Journal Article↗
PubMed1992

Effects on the rabbit coronary artery of LP-805, a new type of releaser of endothelium-derived relaxing factor and a K+ channel opener.

In the rabbit epicardial coronary artery, 8-tert-butyl-6,7-dihydropyrolo[3,2-e]5-methylpyrazolo [1,5-a]pyrimidine-3-carbonitrile (LP-805, greater than 0.1 microM) hyperpolarized the muscle membrane in both proximal (diameter, 1-1.2 mm) and distal (diameter, 0.1-0.2 mm) regions of intact (+E) tissue, in which endothelium is present, and endothelium-denuded (-E) tissue. LP-805-induced hyperpolarization was inhibited by glibenclamide. In -E tissues in both regions, acetylcholine (ACh, greater than 0.1 microM) depolarized the membrane, and LP-805 inhibited the depolarization. However, in +E tissues, ACh (greater than 0.1 microM) transiently hyperpolarized the membrane that was not modified by glibenclamide (10 microM), charybdotoxin (100 nM), and NG-nitro-L-arginine (L-NNA, 100 microM). In -E tissues of both regions, LP-805 consistently inhibited the 10 microM ACh-induced contraction (IC50, 2.8 microM), and 10 microM glibenclamide shifted this concentration-response curve to the right (IC50, 20 microM). In +E tissues, LP-805 more potently inhibited the ACh-induced contraction (IC50, 0.3 microM), and this inhibition was prevented by L-NNA (100 microM) but not by indomethacin or glibenclamide (10 microM). In -E and +E tissues of both regions, LP-805 repolarized the high K(+)-induced depolarization (less than 20 mM) and relaxed the tissues precontracted by high K+ (less than 30 mM); these electrical and mechanical effects of LP-805 were prevented by glibenclamide (10 microM) in +E tissues. In +E tissues, the K(+)-induced contraction (less than 30 mM) was more strongly inhibited than in -E tissues, but after treatment with L-NNA, LP-805 relaxed -E and +E tissues precontracted to the same extent in the presence of high K+. LP-805 (10 microM) did not inhibit the Ca(2+)-induced contraction in skinned muscle tissues but did slightly inhibit the ACh-induced contraction in Ca(2+)-free solution containing 2 mM EGTA. Thus, LP-805 has a potent releasing action on endothelium-derived relaxing factor and also the potential to open the glibenclamide-sensitive K+ channel. These events would account for the dilation of the rabbit coronary artery exposed to LP-805.

Acetylcholine↗
PubMed1991

Effects of protamine on vascular smooth muscle of rabbit mesenteric artery.

Systemic hypotension is commonly observed in association with protamine administration after cardiopulmonary bypass. However, little information is available concerning the action of protamine on vascular smooth muscle. Thus, we investigated the action of protamine on vascular tissues using tension recording and microelectrode methods. Protamine (5-500 micrograms/ml) inhibited contractions induced by norepinephrine (NE)- or elevated K+ in a concentration-dependent manner in both endothelium-intact and -denuded strips. Protamine inhibition of NE contractions was less profound after endothelial denudation, whereas protamine inhibition of K(+)-induced contractions was less affected by prior denudation. In endothelium-intact strips, the protamine-induced inhibition was significantly reduced by inhibitors of the endothelium-derived relaxing factor pathway, including oxyhemoglobin, methylene blue, or NG-nitro-L-arginine, whereas the contractile inhibition was enhanced by superoxide dismutase. In endothelium-denuded strips, protamine inhibited Ca(2+)-induced contraction evoked in Ca(2+)-free solution containing 100 mM K+ and inhibited the NE-induced contraction under the following conditions: 1) in Ca(2+)-free solution; 2) after nifedipine treatment; and 3) after depletion of stored Ca2+ by A23187 or ryanodine. In membrane-permeabilized strips, protamine did not modify Ca(2+)-induced contraction. Protamine (50-500 micrograms/ml) did not modify the membrane potential of either endothelium-intact or -denuded strips. Furthermore, protamine irreversibly impaired acetylcholine-induced endothelium-dependent relaxant response, implying a toxic effect of protamine on the endothelium. We conclude that protamine exerts its inhibition on vascular smooth muscles in both an endothelium-dependent and -independent manner; i.e., the endothelium-dependent component is mediated probably by endothelium-derived relaxing factor, and direct smooth muscle effects are due to the inhibition of both Ca(2+)-influx and the NE-induced Ca2+ release from intracellular stores.

Animals↗