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H A Coleman

Publications and source records attributed to H A Coleman.

At least 19 recordsLinked to original sources
PubMed2001

K+ currents underlying the action of endothelium-derived hyperpolarizing factor in guinea-pig, rat and human blood vessels.

Membrane currents attributed to endothelium-derived hyperpolarizing factor (EDHF) were recorded in short segments of submucosal arterioles of guinea-pigs using single microelectrode voltage clamp. The functional responses of arterioles and human subcutaneous, rat hepatic and guinea-pig coronary arteries were also assessed as changes in membrane potential recorded simultaneously with contractile activity. The current-voltage (I-V) relationship for the conductance due to EDHF displayed outward rectification with little voltage dependence. Components of the current were blocked by charybdotoxin (30-60 nM) and apamin (0.25-0.50 microM), which also blocked hyperpolarization and prevented EDHF-induced relaxation. The EDHF-induced current was insensitive to Ba2+ (20-100 microM) and/or ouabain (1 microM to 1 mM). In human subcutaneous arteries and guinea-pig coronary arteries and submucosal arterioles, the EDHF-induced responses were insensitive to Ba2+ and/or ouabain. Increasing [K+]o to 11-21 mM evoked depolarization under conditions in which EDHF evoked hyperpolarization. Responses to ACh, sympathetic nerve stimulation and action potentials were indistinguishable between dye-labelled smooth muscle and endothelial cells in arterioles. Action potentials in identified endothelial cells were always associated with constriction of the arterioles. 18beta-Glycyrrhetinic acid (30 microM) and carbenoxolone (100 microM) depolarized endothelial cells by 31 +/- 6 mV (n = 7 animals) and 33 +/- 4 mV (n = 5), respectively, inhibited action potentials in smooth muscle and endothelial cells and reduced the ACh-induced hyperpolarization of endothelial cells by 56 and 58 %, respectively. Thus, activation of outwardly rectifying K+ channels underlies the hyperpolarization and relaxation due to EDHF. These channels have properties similar to those of intermediate conductance (IKCa) and small conductance (SKCa) Ca2+-activated K+ channels. Strong electrical coupling between endothelial and smooth muscle cells implies that these two layers function as a single electrical syncytium. The non-specific effects of glycyrrhetinic acid precludes its use as an indicator of the involvement of gap junctions in EDHF-attributed responses. These conclusions are likely to apply to a variety of blood vessels including those of humans.

Animals↗
PubMed2001

EDHF is not K+ but may be due to spread of current from the endothelium in guinea pig arterioles.

Endothelium-derived hyperpolarizing factor (EDHF)-attributed hyperpolarizations and relaxations were recorded simultaneously from submucosal arterioles of guinea pigs with the use of intracellular microelectrodes and a video-based system, respectively. Membrane currents were recorded from electrically short segments of arterioles under single-electrode voltage clamp. Substance P evoked an outward current with a current-voltage relationship that was well described by the Goldman-Hodgkin-Katz equation for a K+ current, consistent with the involvement of intermediate- and small-conductance Ca2+-activated K+ channels. 1-Ethyl-2-benzimidazolinone relaxed the arterioles and evoked hyperpolarizations that were blocked by charybdotoxin, but not by iberiotoxin. Application of K+ induced depolarization under conditions in which EDHF evoked hyperpolarization. The Ba2+-sensitive component of the K+-induced current was inwardly rectifying, in contrast to the outwardly rectifying current evoked by substance P. EDHF-attributed hyperpolarizations in dye-identified smooth muscle cells were indistinguishable from those recorded from dye-identified endothelial cells in the same arterioles. These results provide evidence that EDHF is not K+ but may involve electrotonic spread of hyperpolarization from the endothelial cells to the smooth muscle cells.

Acetylcholine↗
PubMed2000

Changes in the mechanisms involved in uterine contractions during pregnancy in guinea-pigs.

1. The mechanisms involved in contraction in guinea-pig myometrium were compared at mid- and late pregnancy. Tension was recorded simultaneously with either membrane potential or cytoplasmic calcium ([Ca2+]i) in strips exposed briefly to prostaglandin F2alpha (PGF). 2. PGF-induced increases in tension were underpinned by action potentials followed by sustained depolarization and biphasic increases in [Ca2+]i at mid- (peak, 879 +/- 199 nM; sustained, 298 +/- 35 nM, n = 11) and late pregnancy (peak, 989 +/- 302 nM; sustained 178 +/- 33 nM, n = 8). 3. At mid- and late pregnancy, nifedipine (10-6 M) reduced (a) the PGF-induced increase in tension to 84 and 35 %, (b) the level attained during the depolarization by 2 and 12 mV and (c) the peak rise in [Ca2+]i to 42 and 17 %. The sustained rises in [Ca2+]i were resistant to nifedipine. 4. In Ca2+-free solution (containing 1 mM EGTA), PGF elicited an increase in tension that was 26 % of that in 2.5 mM Ca2+ and an increase in [Ca2+]i (24 % of the sustained level) at mid-pregnancy but no increase in tension or [Ca2+]i at term. 5. At both stages of pregnancy, PGF decreased the level of [Ca2+]i required to elicit increases in tension comparable to those evoked by high K+o. The slope of the tension-[Ca2+]i curves were steeper in mid- than in late pregnancy. 6. In conclusion, at mid-pregnancy, the contractile response of the guinea-pig myometrium to PGF involves Ca2+ influx through L-type voltage-operated Ca2+ channels (VOCCs) and by receptor-operated mechanisms, release of Ca2+ from intracellular stores, and an increase in the sensitivity of the contractile apparatus to Ca2+. At term the situation is different: a modest increase in the sensitivity of the contractile apparatus to Ca2+ persists and there is a major reliance on Ca2+ influx through VOCCs.

Animals↗
PubMed2000

EDHF, NO and a prostanoid: hyperpolarization-dependent and -independent relaxation in guinea-pig arteries.

The contribution of endothelium-derived hyperpolarizing factor (EDHF), nitric oxide (NO) and a prostanoid (PG) to endothelium-dependent hyperpolarization and relaxation were assessed in coronary and mammary arteries of guinea-pigs by integration of the responses evoked during discrete applications of acetylcholine (ACh). The results of this integration approach were compared with those using traditional peak analysis methods. N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) and indomethacin (1 microM), alone or in combination, were without effect on peak hyperpolarizations or relaxations while they markedly reduced the integrated responses in both arteries. Integrated responses attributed to NO and PG were larger than those attributed to EDHF in the coronary artery (at 2 microM ACh, hyperpolarization (mV s): NO, 4200+/-91; PG, 5046+/-157; EDHF, 1532+/-94; relaxation (mN s mm(-1)): NO, 2488+/-122; PG, 2234+/-96; EDHF, 802+/-54). Integrated responses attributed to NO, PG and EDHF were similar in the mammary artery (at 2 microM ACh, hyperpolarization: NO, 347+/-69; PG, 217+/-49; EDHF, 310+/-63; relaxation: NO, 462+/-94; PG, 456+/-144; EDHF, 458+/-40). Gilbenclamide (1 microM) all but abolished the hyperpolarization attributable to NO and PG but not EDHF in both arteries allowing assessment of the role of the hyperpolarization in relaxation. Gilbenclamide was without effect on the integrated relaxation due to NO but significantly reduced the relaxation associated with PG in the two arteries. In conclusion, integration of the responses enabled a more complete assessment of the contribution of EDHF, NO and PG to endothelium-dependent responses, which were strikingly different in the two arteries. There is commonality in the role of hyperpolarization in relaxation in both arteries: EDHF-dependent relaxation is strongly dependent on hyperpolarization; hyperpolarization plays an important role in PG relaxation, whereas it has a small facilitatory role in NO-dependent relaxation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Hyperpolarization and slowing of the rate of contraction in human uterus in pregnancy by prostaglandins E2 and f2alpha: involvement of the Na+ pump.

1. The effects of prostaglandins E2 (PGE) and F2alpha (PGF) on membrane potential and isometric tension and cytoplasmic free calcium concentration ([Ca2+]i) and tension were studied in strips of uterine smooth muscle obtained from women undergoing Caesarean delivery at term and during established labour. 2. Prostaglandins (PGs) evoked a biphasic response. The excitatory component consisted of depolarization of the membrane, which initiated spike action potentials, an increase in [Ca2+]i and tension development. The membrane remained depolarized at -19 +/- 1 mV for about 2 min, then repolarized abruptly, [Ca2+]i promptly returned to basal levels, and tension development ceased. 3. This component of the response to PGE or PGF was followed by a slow hyperpolarization which reached -85 +/- 2 mV (n = 22) at term and -70 +/- 2 mV (n = 9) during labour, and during which spontaneous action potentials and tension development did not occur. 4. Nifedipine (10-6 M) abolished spontaneous activity, abolished PG-induced action potentials and reduced the increase in [Ca2+]i (9 +/- 3 %, n = 6), the depolarization (10 +/- 1 mV, n = 14), the tension (2 +/- 1 %, n = 14) and the hyperpolarization (9 +/- 1 mV, n = 14, at term). 5. A variety of K+ channel blockers were without effect on the peak amplitude of the PG-induced hyperpolarization but the latter did not occur in the presence of ouabain (10-6 M) or in K+-free or low-Na+ solutions, suggesting an involvement of the Na+-K+-ATPase pump. 6. In conclusion, a substantial dependence on Ca2+ influx through voltage-operated Ca2+ channels accounts for the importance of membrane potential in regulating contractions in human uterine smooth muscle. The classical excitatory effect of PGE and PGF is followed by hyperpolarization involving the Na+-K+-ATPase pump. The hyperpolarization restricts the response to a single contraction and decreases the frequency of subsequent contractions. The amplitude of the hyperpolarization decreases during labour, allowing contraction frequency to increase. Its persistence at this time ensures complete relaxation between each single robust contraction, preventing spasm of the uterus that would restrict blood flow to the fetus during delivery.

Albuterol↗
PubMed1999

Contractile activity, membrane potential, and cytoplasmic calcium in human uterine smooth muscle in the third trimester of pregnancy and during labor.

OBJECTIVE: This study was undertaken to investigate in human tissue samples the mechanisms underlying spontaneous and prostaglandin F(2)(alpha)-induced contractions during the final trimester of pregnancy and labor. STUDY DESIGN: Membrane potential and cytoplasmic calcium were recorded simultaneously with contraction in uterine strips obtained from the lower segment during cesarean delivery. RESULTS: Between week 28 of gestation and term there was a progressive increase in the frequency of spontaneous contractions and a decrease in the negative potential of the membrane. The response to prostaglandin F(2alpha) was biphasic. The initial excitatory component remained stable toward term. A later inhibitory component, which was underpinned by increased activity of the sodium-potassium adenosine triphosphatase pump, decreased at the time of labor. CONCLUSIONS: There is a gradual increase in excitability in uterine muscle throughout the third trimester of human pregnancy. The initial component of the prostaglandin response is a large contraction that is kept brief by a subsequent inhibitory component of the response, which ensures that full relaxation occurs between contractions.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

Endothelium-dependent hyperpolarization in resting and depolarized mammary and coronary arteries of guinea-pigs.

1. The membrane potential responses in guinea-pig coronary and mammary arteries attributable to endothelium-derived nitric oxide (NO), prostaglandin (PG) and hyperpolarizing factor (EDHF), and to exogenous NO and the prostacyclin analogue, iloprost, were compared at rest and when depolarized with the thromboxane analogue, U46619. 2. In the coronary artery, stimulation of the endothelium with acetylcholine (ACh) evoked hyperpolarization attributable to NO and a PG with similar pD2s at rest and in the presence of U46619. However, in depolarized tissues, the pD2 of the response attributed to EDHF required a 10 fold lower concentration of ACh compared with at rest. 3. In the mammary artery, lower concentrations of ACh were required to evoke NO- and EDHF-dependent hyperpolarizations in depolarized mammary artery compared with at rest, while PG-dependent hyperpolarization did not occur until the concentration of ACh was increased some 10 fold both at rest and in U46619. 4. The smooth muscle of the coronary artery of guinea-pigs was some 4 fold more sensitive to exogenous NO and iloprost than was the mammary artery. 5. In conclusion, the membrane potential response in arteries at rest, that is, in the absence of constrictor, may be extrapolated to events in the presence of constrictor when NO and PG are under study. However, the sensitivity to ACh and the magnitude of the hyperpolarization attributed to EDHF obtained in tissues at rest may underestimate these parameters in depolarized tissues.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Muscarinic receptor activation in guinea-pig chromaffin cells causes decreased membrane conductance and depolarization.

Membrane potentials were recorded with conventional intracellular microelectrodes from chromaffin cells in isolated, bisected adrenal glands from guinea-pigs. The local pressure ejection of muscarinic agonists, acetylcholine (in the presence of hexamethonium) or bethanecol, caused a transient depolarization that was relatively slow (1-2 s) in onset compared with the depolarization associated with the activation of nicotinic receptors. Muscarinic receptor-induced depolarization was associated with an increase in input resistance and the firing of action potentials. Repetitive stimulation of splanchnic nerve fibers within the gland, in the presence of hexamethonium, caused a maintained depolarization that was slow in both onset and decay and in many cells caused the repetitive firing of action potentials. It is suggested that, in this species, the exocytosis of catecholamines caused by the activation of muscarinic receptors, described by others, may be due to the initiation of tetrodotoxin-sensitive action potentials and consequent opening of voltage sensitive Ca2+ channels.

Acetylcholine↗
PubMed1996

The association between melatonin production and electrophysiology of the guinea pig pineal gland.

Melatonin production by isolated pineal glands from guinea pigs was examined under conditions that affect membrane potential or the firing of action potential-like spikes. In glands from superior cervical ganglionectomized animals, depolarization resulting from increasing extracellular potassium concentration to 100 mM did not initiate melatonin production, and it delayed the response to the beta-adrenoceptor agonist orciprenaline. In glands from intact animals melatonin production was initiated by exposure to 100 mM potassium with a time-course similar to the response to orciprenaline. A proportion of this response was propanol resistant, suggesting that the normal control of melatonin production may involve a neurotransmitter in addition to norepinephrine. Exposure to verapamil or nifedipine, or removal of extracellular calcium, previously shown to eliminate action potential-like spikes, did not substantially affect the increase in melatonin production induced by orciprenaline. Phenylephrine, which stimulates spiking, produced only a slight increase in melatonin production. It is concluded that the depolarization and the spiking are not closely related to the stimulation of melatonin production, but may relate principally to the secretion of a substance other than melatonin.

Adrenergic alpha-Agonists↗
PubMed1995

Role of membrane potential in endothelium-dependent relaxation of guinea-pig coronary arterial smooth muscle.

1. Membrane potential and tension were measured simultaneously in ring segments of main coronary artery of guinea-pigs. The synthetic thromboxane A2 analogue U46619 depolarized the tissues from -58 +/- 2 to -40 +/- 1 mV and increased tension by 12 +/- 1 mN mm-1. Nitric oxide (NO) and Iloprost, the stable analogue of prostacyclin, evoked hyperpolarization and relaxation. 2. The concentration of NO required to evoke half-maximal hyperpolarization (EC50 of 2 x 10(-5) M) was 40-fold higher than that which was required to induce relaxation (EC50 of 5 x 10(-7) M). The EC50 for Iloprost-induced hyperpolarization (3 x 10(-8) M) was similar to that for relaxation (4 x 10(-8) M). 3. Glibenclamide (10(-6) M) abolished the hyperpolarization in response to both NO and Iloprost but was without effect on the amplitudes of the relaxations over the complete concentration-response curves. 4. Acetylcholine evoked concentration-dependent hyperpolarization and relaxation in the presence of N omega-nitro-L-arginine methyl ester (NAME; 10(-5) M) and indomethacin (10(-6) M), and these responses were attributed to endothelium-derived hyperpolarizing factor (EDHF). The hyperpolarization produced by EDHF always preceded relaxation, and relaxation never occurred at concentrations of acetylcholine that were insufficient to evoke hyperpolarization. 5. The concentration-hyperpolarization and concentration-relaxation curves in response to acetylcholine were not affected by glibenclamide or barium (1-3 mM) but were shifted to the right 4- and 5-fold, respectively, by 1 mM tetraethylammonium. The hyperpolarization and relaxation evoked by acetylcholine were also reduced in a parallel manner when the potassium concentration in the superfusate was increased. 6. Hyperpolarizing current steps, applied to spiral strips of coronary artery denuded of endothelium and depolarized and constricted with U46619, caused relaxation. The relationship between hyperpolarization and relaxation evoked electronically was similar to that which was due to EDHF in intact tissues stimulated with acetylcholine. 7. It is concluded that the ability of NO or Iloprost to relax guinea-pig coronary artery does not depend upon hyperpolarization of the smooth muscle. In contrast, hyperpolarization is likely to play a major, if not the only, role in the relaxation in response to EDHF in this tissue.

Acetylcholine↗
PubMed1995

Tetrodotoxin-sensitive action potentials in smooth muscle of mouse vas deferens.

Action potentials were recorded during impalements of some but not all smooth muscle cells of mouse vas deferens in response to both nerve stimulation and intracellular current injection. They were resistant to blockade by nifedipine (0.1-1.0 microM) but were blocked by tetrodotoxin (TTX, 0.2-1.0 microM) when this was added in the presence of nifedipine. It is suggested that voltage-dependent sodium (Na+) channels are present in mouse vas deferens that function to amplify calcium (Ca2+) influx through voltage-dependent Ca2+ channels.

Action Potentials↗
PubMed1995

Currents caused by the spontaneous release of quanta of acetylcholine onto chromaffin cells in guinea-pig adrenal medulla.

Membrane potentials were recorded from chromaffin cells in isolated bisected adrenal glands from guinea-pigs. Spontaneous excitatory synaptic potentials (SESPs) were recorded whose frequency was increased following brief (up to 10 s) periods of presynaptic nerve stimulation at 10-30 Hz. The single electrode voltage-clamp method was used to record the currents underlying all but the largest SESPs. Spontaneous excitatory synaptic currents (SESCs) decayed according to a single exponential with a time constant of about 8 ms at 30 degrees C. Thus the neuronal nicotinic receptor-channels giving rise to SESCs in chromaffin cells are probably very similar to those that are opened by quanta of acetylcholine in sympathetic ganglion cells.

Acetylcholine↗
PubMed1995

Release of endothelium-derived hyperpolarizing factor (EDHF) by M3 receptor stimulation in guinea-pig coronary artery.

1. The muscarinic receptor subtype(s) involved in the release of endothelium-derived hyperpolarizing factor (EDHF) were studied in the guinea-pig coronary artery by recording the membrane potential in the smooth muscle cells with intracellular microelectrodes. 2. Acetylcholine (ACh, pD2 6.68) was 10 times more potent than the M2 agonist, oxotremorine (pD2 5.65) and 500 fold more potent than the M1 agonist, McN-A-343 (pD2 3.95) in evoking the EDHF hyperpolarization. 3. The M3 muscarinic antagonist, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) was the most potent (pA2 9.5) in inhibiting the release of EDHF evoked by ACh, being more potent than pirenzepine (pA2 6.7), and AFDX-116 (pA2 6.1) which preferentially block M1 and M2 receptors, respectively. 4. These results suggest that EDHF is released from the endothelium of the guinea-pig coronary artery upon the activation of the muscarinic M3 receptor subtype.

Animals↗
PubMed1994

Synaptic transmission from splanchnic nerves to the adrenal medulla of guinea-pigs.

1. Membrane potentials were recorded with conventional intracellular microelectrodes from chromaffin cells in isolated, bisected adrenal glands from guinea-pigs. 2. All cells were electrically excitable and responded to depolarizing current with all-or-nothing action potentials that were blocked by tetrodotoxin. 3. Input resistance was 180 +/- 14 M omega and this was lower than that reported for isolated chromaffin cells using patch electrodes. 4. All cells responded to transmural stimulation with action potentials that arose from excitatory synaptic potentials in response to the excitation of one or more preganglionic fibres, many having strong synaptic action. Other fibres had weaker synaptic action but in all cases, maximal transmural stimulation caused depolarization well above threshold for action potential initiation. 5. Spontaneous excitatory synaptic potentials were observed whose frequency was greatly increased by repetitive stimulation at 10 or 30 Hz. 6. No evidence was found for the desensitization of nicotinic receptors in response to acetylcholine released from presynaptic nerve terminals. 7. These experiments show that there are many similarities between the responses to splanchnic nerve stimulation of guinea-pig chromaffin cells in situ and sympathetic ganglion cells from the same species.

Action Potentials↗
PubMed1994

Pilocarpine-induced relaxation of rat tail artery by a non-cholinergic mechanism and in the absence of an intact endothelium.

1. The partial muscarinic agonist, pilocarpine, evoked concentration-dependent relaxation with an EC50 of 2.4 x 10(-3) M in isolated segments of rat tail artery that were constricted with phenylephrine (10(-8) to 2 x 10(-7) M). Acetylcholine also evoked concentration-dependent relaxation but was more potent than pilocarpine (EC50, 6.5 x 10(-7) M). 2. The concentration-relaxation curves for pilocarpine were not affected by the muscarinic antagonists, atropine (10(-9) M) or pirenzepine (5 x 10(-7) M), while the concentration-relaxation curves for acetylcholine-evoked relaxation of the same tissues were shifted some 10 fold to the right by these concentrations of atropine and pirenzepine. 3. Acetylcholine failed to evoke relaxation following removal of the endothelium. The smooth muscle of the rat tail artery was some 10 fold more sensitive to the relaxing action of pilocarpine following denudation of the endothelium. 4. The effects of pilocarpine and acetylcholine on membrane potential were studied in tissues that were depolarized to -39 +/- 1 mV with phenylephrine (5 x 10(-8) to 2 x 10(-7) M). In intact tissues, pilocarpine caused hyperpolarization, an effect that persisted in the presence of muscarinic antagonists. Acetylcholine also evoked hyperpolarization. 5. Following removal of the endothelium, pilocarpine (10(-5) to 10(-3) M) evoked hyperpolarization in 6 of 15 preparations and a decrease in the frequency of action potentials in the remainder. Both of these responses were associated with relaxation. 6. The effects of pilocarpine were compared with other agents that evoke endothelium-independent relaxation. The concentration-relaxation curves in response to pilocarpine and nitroprusside were shifted to the right by ferricyanide (10-5 M) and methylene blue (10-5 M). Glibenclamide (10-6 M) was without effect on the hyperpolarization and relaxation evoked by pilocarpine (10' to 10- M).7. Thus, pilocarpine evokes relaxation of rat tail artery independently of the cholinergic system and it is suggested that this is achieved by decreasing the frequency of action potentials in the smooth muscle.

Acetylcholine↗
PubMed1993

Stretch revealed three components in the hyperpolarization of guinea-pig coronary artery in response to acetylcholine.

1. Membrane potential was recorded with intracellular microelectrodes from the smooth muscle of coronary arteries of guinea-pigs, and the responses to endothelium-derived relaxants were studied under a variety of conditions. 2. Stimulation of the endothelium with brief applications of acetylcholine or substance P evoked concentration-dependent hyperpolarizations that were complex in nature. A transient component, which is likely to result from endothelium-derived hyperpolarizing factor (EDHF), was followed by a slow component that resulted from the production of nitric oxide (NO) and a prostaglandin. 3. The ability of exogenous and endogenous NO and prostacyclin to hyperpolarize the membrane depended upon the smooth muscle being under stretch. Unstretched preparations responded to acetylcholine with only the transient component of hyperpolarization; NO and prostacyclin were without effect. 4. In stretched preparations exogenous NO and prostacyclin, and its synthetic analogue methyl prostacyclin (Iloprost), evoked hyperpolarization, and the slow component of the response induced by acetylcholine appeared. The amplitudes of these responses reached maximum when the tissues were stretched to the equivalent of approximately 50 mmHg. 5. From a resting membrane potential of -61 +/- 0.6 mV, exogenous NO and Iloprost hyperpolarized the smooth muscle to around -80 mV. The EC50 values for NO- and Iloprost-induced hyperpolarization were 2.6 x 10(-6) and 1.3 x 10(-8) M, respectively. 6. Coronary arterial smooth muscles from rats, rabbits and sheep also hyperpolarized in response to exogenous NO, although their sensitivities were less than those of preparations obtained from guinea-pigs. Iloprost hyperpolarized tissues from rabbits and sheep but not those obtained from rats. 7. It is concluded that the endothelial lining of coronary arteries can release three factors, EDHF, NO and prostacyclin, all of which can hyperpolarize the membrane of the smooth muscle. The relative proportions and significance of each factor depends on the amount of stretch, on the artery and on the species of animal.

Acetylcholine↗