scholarly journals Endothelial Nitric Oxide Suppresses Action-Potential-Like Transient Spikes and Vasospasm in Small Resistance Arteries

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 785-794
Author(s):  
Josh F. Smith ◽  
Hamish A.L. Lemmey ◽  
Lyudmyla Borysova ◽  
C. Robin Hiley ◽  
Kim A. Dora ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Quantitative Polymerase Chain Reaction ◽  
Mesenteric Arteries ◽  
Muscle Membrane ◽  
Myogenic Tone ◽  
Resistance Arteries ◽  
Spontaneously Hypertensive ◽  
Small Arteries ◽  
Smooth Muscle Membrane

Endothelial dysfunction in small arteries is a ubiquitous, early feature of cardiovascular disease, including hypertension. Dysfunction reflects reduced bioavailability of endothelium-derived nitric oxide (NO) and depressed endothelium-dependent hyperpolarization that enhances vasoreactivity. We measured smooth muscle membrane potential and tension, smooth muscle calcium, and used real-time quantitative polymerase chain reaction in small arteries and isolated tubes of endothelium to investigate how dysfunction enhances vasoreactivity. Rat nonmyogenic mesenteric resistance arteries developed vasomotion to micromolar phenylephrine (α 1 -adrenoceptor agonist); symmetrical vasoconstrictor oscillations mediated by L-type voltage-gated Ca 2+ channels (VGCCs). Inhibiting NO synthesis abolished vasomotion so nanomolar phenylephrine now stimulated rapid, transient depolarizing spikes in the smooth muscle associated with chaotic vasomotion/vasospasm. Endothelium-dependent hyperpolarization block also enabled phenylephrine-vasospasm but without spikes or chaotic vasomotion. Depolarizing spikes were Ca 2+ -based and abolished by either T-type or L-type VGCCs blockers with depressed vasoconstriction. Removing NO also enabled transient spikes/vasoconstriction to Bay K-8644 (L-type VGCC activator). However, these were abolished by the L-type VGCC blocker nifedipine but not T-type VGCC block. Phenylephrine also initiated T-type VGCC-transient spikes and enhanced vasoconstriction after NO loss in nonmyogenic arteries from spontaneously hypertensive rats. In contrast to mesenteric arteries, myogenic coronary arteries displayed transient spikes and further vasoconstriction spontaneously on loss of NO. T-type VGCC block abolished these spikes and additional vasoconstriction but not myogenic tone. Therefore, in myogenic and nonmyogenic small arteries, reduced NO bioavailability engages T-type VGCCs, triggering transient depolarizing spikes in normally quiescent vascular smooth muscle to cause vasospasm. T-type block may offer a means to suppress vasospasm without inhibiting myogenic tone mediated by L-type VGCCs.

KCa-channel blockade prevents sustained pressure-induced depolarization in rat mesenteric small arteries

1997 ◽  
Vol 272 (5) ◽  
pp. H2241-H2249 ◽  
Author(s):  
J. P. Wesselman ◽  
R. Schubert ◽  
E. D. VanBavel ◽  
H. Nilsson ◽  
M. J. Mulvany
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Transmural Pressure ◽  
Muscle Membrane ◽  
Outer Diameter ◽  
Small Arteries ◽  
Pressure Elevation ◽  
Kca Channels ◽  
Smooth Muscle Membrane

In small blood vessels, elevation of transmural pressure induces myogenic constrictions and smooth muscle depolarization. The role of calcium-activated K+ channels (KCa channels) in these responses was examined in cannulated rat mesenteric small arteries. Inner and outer diameter were continuously monitored with a video technique. Smooth muscle membrane potential was recorded simultaneously using microelectrodes. To test for myogenic responsiveness, the transmural pressure was changed stepwise in the range between 10 and 120 mmHg. Pressure elevation induced moderate myogenic responses and significant depolarization, from -54.5 +/- 0.4 (SE) mV (n = 56) at 10 mmHg to -47.3 +/- 1.8 mV (n = 12) at 120 mmHg. Norepinephrine (NE, 0.67 and 10 microM) induced constriction and vasomotion, augmented myogenic responsiveness, and shifted the pressure-membrane potential relation to more depolarized values. Blockade of the Kca channels with charybdotoxin (ChTX) suppressed the responsiveness to pressure. In the absence of ChTX, with 0.67 microM NE, pressure elevation from 10 to 120 mmHg induced depolarization from -46.9 +/- 1.0 (n = 16) to -35.8 +/- 0.7 (n = 12) mV, whereas because of the myogenic response, the diameter increased only by 7%. In the presence of ChTX, with 0.3 microM NE, pressure changed the membrane potential from -41.0 +/- 1.1 (n = 12) to -37.8 +/- 0.7 mV (n = 4), which was not significant, and the diameter increased by 28%. These results demonstrate that blockade of KCa channels reduces responsiveness to pressure elevation. This suggests that pressure may induce depolarization and concomitant myogenic responsiveness by closure of KCa channels.

The relation between the structure and innervation of small arteries and arterioles and the smooth muscle membrane potential changes expected at different levels of sympathetic nerve activity

1983 ◽  
Vol 220 (1219) ◽  
pp. 237-249 ◽  
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Membrane ◽  
Nerve Activity ◽  
Release Of Noradrenaline ◽  
Small Arteries ◽  
Perivascular Nerves ◽  
Smooth Muscle Membrane

The membrane potential changes in arterial smooth muscle due to natural sympathetic nerve activity have been calculated. The electrical properties of the smooth muscle syncytium were taken into account and various assumptions made concerning the release of noradrenaline by the perivascular nerves. The depolarization that would result from asynchronous nerve activity at various mean frequencies was calculated for arterioles and small arteries of various diameters up to 150 μm. The calculations suggested that the depolarization would be irregular and that discrete excitatory junction potentials as evoked by synchronous nerve stimulation would not be recorded during natural nerve activity. The irregularity of the depolarization would be greater in small arterioles and would cause them to reach threshold for action potential generation at lower frequencies of nerve activity than larger arteries.

Properties of smooth muscle hyperpolarization and relaxation to K+ in the rat isolated mesenteric artery

2001 ◽  
Vol 280 (6) ◽  
pp. H2424-H2429 ◽  
Author(s):  
Kim A. Dora ◽  
Christopher J. Garland
Keyword(s):  
Smooth Muscle ◽  
Mesenteric Artery ◽  
Muscle Relaxation ◽  
Relaxation Curve ◽  
Mesenteric Arteries ◽  
Muscle Membrane ◽  
Smooth Muscle Relaxation ◽  
Smooth Muscle Membrane ◽  
Inner Diameter ◽  
The Right

Smooth muscle membrane potential and tension in rat isolated small mesenteric arteries (inner diameter 100–200 μm) were measured simultaneously to investigate whether the intensity of smooth muscle stimulation and the endothelium influence responses to exogenous K+. Variable smooth muscle depolarization and contraction were stimulated by titration with 0.1–10 μM phenylephrine. Raising external K+ to 10.8 mM evoked correlated, sustained hyperpolarization and relaxation, both of which were inhibited as the smooth muscle depolarized and contracted to around −38 mV and 10 mN, respectively. At these higher levels of stimulation, raising the K+ concentration to 13.8 mM still hyperpolarized and relaxed the smooth muscle. Relaxation to endothelium-derived hyperpolarizing factor, released by ACh, was not altered by the level of stimulation. In endothelium-denuded arteries, the concentration-relaxation curve to K+ was shifted to the right but was not depressed. In denuded arteries, relaxation to K+ was unaffected by the extent of prior stimulation and was blocked with 0.1 mM ouabain but not with 30 μM Ba2+. The ability of K+ to stimulate simultaneous hyperpolarization and relaxation in the mesenteric artery is consistent with a role as an endothelium-derived hyperpolarizing factor activating inwardly rectifying K+ channels on the endothelium and Na+-K+-ATPase on the smooth muscle cells.

Nitric oxide: mediator of NANC hyperpolarization of opossum esophageal smooth muscle

1991 ◽  
Vol 261 (6) ◽  
pp. G1012-G1016 ◽  
Author(s):  
C. Du ◽  
J. Murray ◽  
J. N. Bates ◽  
J. L. Conklin
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Muscle Membrane ◽  
Circular Smooth Muscle ◽  
Electrical Pulses ◽  
Smooth Muscle Membrane ◽  
Transmembrane Potential Difference ◽  
Oxide Synthase

Activation of intrinsic nonadrenergic noncholinergic (NANC) esophageal nerves during peristalsis or by electrical field stimulation (EFS) in vitro produces a hyperpolarization followed by a depolarization of the circular smooth muscle of the opossum esophagus. N omega-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase, and nitric oxide (NO) were used to test the hypothesis that NO or a NO-containing compound is a mediator of this NANC nerve-induced hyperpolarization of circular esophageal smooth muscle. The transmembrane potential difference of esophageal circular smooth muscle cells was recorded with glass microelectrodes. Nerve-mediated membrane responses were evoked by single electrical pulses of 0.5 ms duration and 50 V amplitude. L-NNA abolished the initial hyperpolarization and reduced the amplitude of and the time to maximal depolarization. L-Arginine (1 mM), the substrate for NO synthase, antagonized the effect of L-NNA. Exogenous NO produced hyperpolarization of the smooth muscle membrane potential and attenuated the amplitudes of EFS-induced hyperpolarization and depolarization. The effect of NO was blocked neither by L-NNA nor by tetrodotoxin (1 microM). The data support the hypothesis that NO or a NO-containing compound mediates NANC nerve-induced responses of the esophageal smooth muscle membrane.

Gender-dependent modulation of α1-adrenergic responses in rat mesenteric arteries

2003 ◽  
Vol 284 (5) ◽  
pp. H1737-H1743 ◽  
Author(s):  
Alyson P. McKee ◽  
Dee A. Van Riper ◽  
Cathy A. Davison ◽  
Harold A. Singer
Keyword(s):  
Smooth Muscle ◽  
Endothelial Damage ◽  
Selective Inhibitor ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Adrenergic Agonist ◽  
Contractile Responses ◽  
Cyclooxygenase 1 ◽  
Acid Metabolites ◽  
Selective Increase

The purpose of this study was to test the hypothesis that pathways modulating vasoconstriction in rat mesenteric resistance arteries are gender dependent. Net contractile responses to phenylephrine were significantly increased by endothelium disruption in arteries from males but not females. This gender-dependent effect was stimulus specific, because disruption of endothelium increased reactivity to serotonin comparably in arteries from both genders. Ovariectomy unmasked an increase in net α1-adrenergic contractile responsiveness after endothelium disruption, suggesting α1-adrenergic-stimulated production of endothelial vasodilators is suppressed in control females by gonadal sex steroids. Production of modulatory endothelium-derived vasodilators in males is balanced by production of vasoconstricting arachidonic acid metabolites. This was revealed by decreased α1-adrenergic contractile responses in arteries from males after pretreatment with indomethacin or the cyclooxygenase-1 selective inhibitor SC-560. The indomethacin-induced effect persisted after endothelium disruption, indicating smooth muscle as the source of cyclooxygenase-1-derived vasoconstrictors and was attenuated after orchiectomy. This study indicates gender differences in the expression of two pathways modulating α1-adrenergic sensitivity in mesenteric arteries: an endothelium-dependent vasodilator pathway and a balancing smooth muscle cyclooxygenase-1-dependent vasoconstrictor pathway. One consequence of these differences is that endothelial damage produces a selective increase in α1-adrenergic agonist reactivity in arteries from males.

Endothelium-dependent hyperpolarization elicited by adenine compounds in rabbit carotid artery

1991 ◽  
Vol 260 (4) ◽  
pp. H1037-H1042 ◽  
Author(s):  
G. Chen ◽  
H. Suzuki
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Direct Action ◽  
Smooth Muscles ◽  
Muscle Membrane ◽  
Dependent Manner ◽  
Rabbit Carotid Artery ◽  
Mechanical Removal ◽  
Smooth Muscle Membrane ◽  
Adventitial Cells

Electrical responses of the membrane of intimal and adventitial smooth muscle cells of the rabbit carotid artery to ATP, ADP, AMP, and adenosine were recorded. In intimal cells, these compounds hyperpolarized the membrane. Mechanical removal of the endothelium altered the responses to ATP and ADP to one of a transient depolarization, with no alteration of the response to AMP and adenosine. In the adventitial cells, ATP and ADP produced a transient depolarization, whereas AMP and adenosine produced a sustained hyperpolarization, irrespective of the presence or absence of the endothelium. In tissues with an intact endothelium, 5'-adenylylimidodiphosphate tetralithium salt and alpha,beta-methylene ATP (mATP) transiently depolarized the membrane in these smooth muscles. In case of stabilization with mATP, only hyperpolarization was generated by ATP, in an endothelium-dependent manner. Our interpretation of these observations is that 1) ATP and ADP depolarize smooth muscle membrane by a direct action and hyperpolarize the membrane indirectly through the release of endothelium-derived hyperpolarizing factor, 2) AMP and adenosine hyperpolarize the membrane, independently of the endothelium, and 3) ATP receptors present on the endothelial cell membrane differ from those on smooth muscle membrane.

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