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Biomedical subjects

W J Stekiel

Publications and source records attributed to W J Stekiel.

At least 19 recordsLinked to original sources
PubMed2001

Mechanisms of isoflurane-mediated hyperpolarization of vascular smooth muscle in chronically hypertensive and normotensive conditions.

BACKGROUND: The purpose of this study was to compare the effects of isoflurane on membrane and intracellular mechanisms that regulate vascular smooth muscle (VSM) transmembrane potential (Em; which is related to VSM tone) in the spontaneously hypertensive rat (SHR) model of essential hypertension and its normotensive Wistar-Kyoto (WKY) control. METHODS: Vascular smooth muscle Em values were measured in situ in locally denervated, superfused, intact, small (200-300-microm OD) mesenteric arteries and veins in anesthetized 9-12-week-old SHR and WKY. Effects of 1.0 minimum alveolar concentration (0.60 mM) superfused isoflurane on VSM Em were measured before and during superfusion with specific inhibitors of VSM calcium-activated (KCa) and adenosine triphosphate-regulated (KATP) potassium channels, and with endogenous mediators of vasodilatation (nitric oxide, cyclic guanosine monophosphate, protein kinase G, cyclic adenosine monophosphate, and protein kinase A). RESULTS: Isoflurane significantly hyperpolarized small arteries (5 +/- 3.4 mV) and veins (6 +/- 4.7 mV) (pooled SHR and WKY, mean +/- SD). Inhibition of KCa and KATP channels, cyclic adenosine monophosphate, and protein kinase A, but not nitric oxide, cyclic guanosine monophosphate, and protein kinase G, abolished such hyperpolarization equally in SHR and WKY vessels. CONCLUSIONS: Isoflurane-induced in situ VSM hyperpolarization in denervated, small mesenteric vessels involves a similar activation of KCa and KATP channels and cyclic adenosine monophosphate, but not nitric oxide or cyclic guanosine monophosphate, second messenger pathways in both SHR and WKY. A greater isoflurane-induced VSM hyperpolarization (observed previously in neurally intact SHR vessels) suggests enhanced inhibition of elevated sympathetic neural input as a major mechanism underlying such hyperpolarization (and coupled relaxation) in this neurogenic model of hypertension.

Anesthetics, Inhalation↗
PubMed2001

Axial stretching of extremity artery induces reversible hyperpolarization of smooth muscle cell membrane in vivo.

Circumferential stretch due to increases in pressure induces vascular smooth muscle cell depolarization and contraction known as the myogenic response. The aim of this study was to determine the in vivo effects of axial-longitudinal stretch of the rat saphenous artery (SA) on smooth muscle membrane potential (Em) and on external diameter. Consecutive elongations of the SA were carried out from resting length (L0) in 10% increments up to 140% L0 while changes in membrane potential and diameter were determined in intact and de-endothelized vessels. Axial stretching resulted in a small initial depolarization at 120% of L0 followed by a progressive 20 to 33% hyperpolarizaion of vascular smooth muscle between 130% and 140% of L0. At 140%, an average maximal 10.6 mV reversible hyperpolarization was measured compared to -41.2 +/- 0.49 mV Em at 100% L0. De-endothelialization completely eliminated the hyperpolarization to axial stretching and augmented the reduction of diameter beyond 120% L0. These results indicate that arteries have a mechanism to protect them from vasospasm that could otherwise occur with movements of the extremities.

Animals↗
PubMed1999

Potassium channel-mediated hyperpolarization of mesenteric vascular smooth muscle by isoflurane.

BACKGROUND: A primary source of calcium (Ca2+) necessary for excitation contraction in vascular smooth muscle (VSM) is influx via voltage-dependent Ca2+ channels. Thus, force generation in VSM is coupled closely to resting transmembrane potential, which itself is primarily a function of potassium conductance. Previously, the authors reported that volatile anesthetics hyperpolarize VSM of small mesenteric resistance arteries and capacitance veins. The current study was designed to determine whether isoflurane-mediated hyperpolarization is the result of specific effects on one or more of four types of potassium channels known to exist in VSM. METHODS: Transmembrane potentials (Em) were recorded from in situ mesenteric capacitance and resistance vessels in Sprague-Dawley rats weighing 250-300 g. In separate experiments, selective inhibitors of each of four types of potassium channels known to exist in VSM were administered in the superfusate of the vessel preparations to assess their effects on isoflurane-mediated hyperpolarization. RESULTS: Resting VSM Em ranged from -38 to -43 mV after local sympathetic denervation. Isoflurane produced a significant hyperpolarization (2.7-4.3 mV), whereas each potassium channel inhibitor significantly depolarized (2.8-8.5 mV) the VSM. Both 100 nM iberiotoxin (inhibitor of high conductance calcium-activated potassium channels) and 1 microM glybenclamide (inhibitor of adenosine triphosphatase-sensitive potassium channels) significantly inhibited VSM hyperpolarization induced by 1 MAC (minimum alveolar concentration) levels of inhaled isoflurane (0.1-0.9 mV Em change, which was not significant). In contrast, isoflurane hyperpolarized the VSM significantly despite the presence of 3 mM 4 aminopyridine (inhibitor of voltage-dependent potassium channels) or 10 microM barium chloride (an inhibitor of inward rectifier potassium channels) (3.7-8.2 mV change in VSM Em). CONCLUSIONS: These results suggest that isoflurane-mediated hyperpolarization (and associated relaxation) of VSM can be attributed in part to an enhanced (or maintained) opening of calcium-activated and adenosine triphosphate-sensitive potassium channels but not voltage-dependent or inward rectifier potassium channels.

Anesthetics, Inhalation↗
PubMed1999

Effect of isoflurane on in situ vascular smooth muscle transmembrane potential in spontaneous hypertension.

BACKGROUND: Administration of general anesthetics to patients with chronic hypertension often causes hemodynamic instability that has been attributed in part to a poorly understood increased loss of control of peripheral vascular smooth muscle tone. The purpose of the current study was to determine if such an increased loss occurs in the spontaneously hypertensive (SH) rat neurogenic model of chronic hypertension, as reflected by a greater volatile anesthetic-induced in situ vascular smooth muscle hyperpolarization compared with normotensive Wistar-Kyoto (WKY) rat controls. METHODS: Vascular smooth muscle transmembrane potentials (E(m)s) were measured in situ using glass microelectrodes in externalized small mesenteric resistance- and capacitance-regulating blood vessels in 10- to 12-week-old SH and WKY rats before, during and after administration of 1 minimum alveolar concentration levels (1.5%) of inhaled or 0.60 mM superfused isoflurane. Vascular smooth muscle E(m)s were also measured in vessels after local sympathetic denervation with superfused 6-hydroxydopamine. RESULTS: Local sympathetic denervation caused a significant hyperpolarization of arterial and venous vascular smooth muscle in SH but not WKY rats. Hyperpolarization induced by either inhaled or superfused isoflurane was significantly greater in innervated than in denervated arterial and venous vascular smooth muscle, particularly in SH rats. In addition, for innervated (but not denervated) arterial and venous vascular smooth muscle, hyperpolarization induced by inhaled (but not superfused) isoflurane was significantly greater in SH than in WKY rats. CONCLUSIONS: In the neurogenic SH rat model of human hypertension, a primary mechanism underlying elevated isoflurane-induced vascular smooth muscle hyperpolarization (and reduced vascular smooth muscle tone) in both resistance- and capacitance-regulating blood vessels is a central neural inhibition of excitatory sympathetic input. Peripheral neural and nonneurally mediated hyperpolarization by isoflurane is similar in SH and WKY rat vascular smooth muscles.

Anesthetics, Inhalation↗
PubMed1998

Effects of volatile anesthetic agents on in situ vascular smooth muscle transmembrane potential in resistance- and capacitance-regulating blood vessels.

INTRODUCTION: This study was designed to compare the inhibitory effect of inhaled volatile anesthetic agents on in situ sympathetic neural versus nonneural regulation of vascular smooth muscle transmembrane potentials as correlates of vascular smooth muscle tone in resistance- and capacitance-regulating blood vessels. METHODS: Vascular smooth muscle transmembrane potentials were measured in situ with glass microelectrodes in neurally intact, small (200-300 m OD) mesenteric arteries and veins of rats before, during, and after inhaled halothane, isoflurane, or sevoflurane (0.5 or 1.0 minimum alveolar concentration [MAC]). Such transmembrane potentials and their anesthetically induced changes were compared, respectively, with those measured in similar vessel preparations after local sympathetic neural denervation with 6-hydroxydopamine. RESULTS: In neurally intact vessels, transmembrane potentials (in millivolts, mean +/- SD) before inhalation of the anesthetic agent were -39 +/- 2.8 (artery) and -43 +/- 4.6 (vein). At 1.0 MAC, halothane, isoflurane, and sevoflurane induced respective hyperpolarizations (in millivolts, mean +/- SD) of 9 +/- 3.1, 6 +/- 2.7, and 9 +/- 4.0 in arteries and 6 +/- 4.4, 2.8 +/- 3.0, and 8.7 +/- 5.6 in veins. Sympathetic denervation significantly attenuated these hyperpolarizations (except for venous response to isoflurane). At 0.5 MAC, transmembrane potential responses to all three volatile anesthetic agents were small and not consistently significant in either the intact or denervated vessels. CONCLUSIONS: In resistance-regulating arteries in situ, inhaled halothane, isoflurane, and sevoflurane (1.0 MAC) attenuate both sympathetic neural and nonneural regulation of vascular smooth muscle transmembrane potentials (and tone). In capacitance-regulating veins in situ, sevoflurane (1.0 MAC) also attenuates both regulatory mechanisms, whereas halothane and isoflurane primarily attenuate nonneural mechanisms. At 0.5 MAC, none of these agents significantly affected either mode of regulation of vascular smooth muscle transmembrane potentials in arteries or veins.

Administration, Inhalation↗
PubMed1996

Effect of halothane and isoflurane on in situ diameter responses of small mesenteric veins to acute graded hypercapnia.

The purpose of the present study was to quantify the inhibitory effect of inhaled halothane and isoflurane on acute hypercapnia-induced responses of capacitance-regulating veins and related cardiovascular variables in response to sequential 40-s periods of 5%, 10%, 15%, and 20% inspired CO2 (FICO2). Measurements were made in normoxic alpha-chloralose-anesthetized rabbits before, during, and after either 0.75 minimum alveolar anesthetic concentration inhaled halothane or isoflurane. The graded hypercapnia caused graded venoconstriction and bradycardia but minimal pressor responses. Hypercapnia-induced venoconstriction was blocked by prior local superfusion of the exposed veins with 3 x 10(-6) M tetrodotoxin. Both the hypercapnia-induced venoconstriction and bradycardia responses were significantly attenuated by halothane or isoflurane and did not fully recover after removal of the anesthetics from the circulation. Both anesthetics produced a significant baseline (i.e., prehypercapnia) hypotension and a tendency toward a resultant tachycardia. The baseline hypotension did not recover completely after elimination of the anesthetic. Neither anesthetic altered baseline vein diameter. These results agree with previous studies demonstrating that hypercapnic acidosis produces mesenteric venoconstriction by elevating excitatory sympathetic efferent neural input via activation of peripheral and central chemoreceptors and that bradycardia results from activation of compensatory baroreflexes. The neural components of these reflexes are possible primary sites for attenuation of these cardiovascular responses by halothane and isoflurane.

Acute Disease↗
PubMed1995

Isoflurane-mediated inhibition of the constriction of mesenteric capacitance veins and related circulatory responses to acute graded hypoxic hypoxia.

We measured the effects of inhaled isoflurane on hypoxemia-induced changes in the diameter of small mesenteric (capacitance-regulating) veins, sympathetic efferent neural activity, heart rate, and arterial blood pressure. Simultaneous changes in these dependent variables were measured in situ in response to 40-s periods of sequentially administered 10%, 5%, 2.5%, and 0% inspired oxygen before, during, and after either 0.75% or 1.5% vol/vol inhaled isoflurane in alpha-chloralose-anesthetized rabbits. Isoflurane inhibited hypoxia-mediated venoconstriction, increases in sympathetic efferent nerve activity, arterial hypertension, and bradycardia. Furthermore, inhibition of diameter, blood pressure, and heart rate responses persisted after washout of isoflurane. Differences in the attenuation of these respective hypoxia-mediated responses were minimal between the two concentrations of inhaled isoflurane. These results further demonstrate that isoflurane alters the ability to produce cardiovascular adjustments to circulatory stress, including changes in vascular capacitance, which is a major regulatory mechanism.

Acute Disease↗
PubMed1995

Responses of cremasteric arterioles of spontaneously hypertensive rats to changes in extracellular K+ concentration.

OBJECTIVE: The goal of this study was to determine the effect of changes in extracellular K+ concentration ([K+]o) on active tone in cremasteric arterioles of spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) and Wistar controls. METHODS: Diameters of third- and fourth-order arterioles were measured in the cremaster muscle of hypertensive and normotensive rats during abrupt changes in superfusate K+ concentration from 4.7 mM to 0 mM to 15 mM K+. RESULTS: Arterioles constricted in response to superfusion with 0 mM K+ and exhibited a large, transient dilation in response to an abrupt change from 0 mM to 15 mM [K+]o. Arteriolar dilation in response to 15 mM K+ was significantly larger in 12-15-week-old SHR than in WKY or Wistar controls. Arteriolar responses to 15 mM K+ were not significantly different in 4-6-week-old SHR and WKY. Dilator responses to 15 mM K+ were generally inhibited by 1 mM ouabain, although ouabain was less effective in inhibiting 15 mM K(+)-induced dilation in arterioles of SHR and WKY than in Wistar rats. CONCLUSIONS: Dilation of cremasteric arterioles in response to 15 mM [K+]o is mediated, at least in part, via stimulation of the electrogenic Na+/K+ pump, although Na+/K(+)-pump-independent components may also contribute to the response. Arterioles of SHR with established hypertension exhibit an altered response to elevated [K+]o which is not present in SHR in the early stage of hypertension.

Animals↗
PubMed1993

Enhanced single-channel K+ current in arterial membranes from genetically hypertensive rats.

Arterial smooth muscle from hypertensive rats shows an increased membrane permeability to K+ that depends on Ca2+ influx. To define the mechanism of this membrane alteration, we tested the hypothesis that Ca(2+)-dependent K+ current (IK(Ca)) is increased in arterial muscle membranes from genetically hypertensive rats. Single-channel K+ currents measured in cell-attached and inside-out aortic membrane patches from spontaneously hypertensive rats (SHR) were compared with those from normotensive Wistar-Kyoto rats (WKY). Inside-out patches from both rat strains showed a predominant 225 pS, Ca(2+)- and voltage-dependent K+ channel in symmetrical 145 mM KCl solutions, which was blocked by tetraethylammonium [concentration for half-maximal block (IC50) < or = 0.3 mM]. In cell-attached patches of aortic muscle cells bathed in physiological salt solution, this channel [IK(Ca) channel] showed a fivefold higher open-state probability (NPo) in SHR as compared with WKY. This increased NPo of SHR IK(Ca) channels in membranes of intact aortic muscle cells was not correlated with an altered membrane potential in current-clamped SHR myocytes or with changes in cytosolic free Ca2+ concentration in fura-2-loaded aortic muscle cells. However, inside-out aortic membrane patches from SHR showed more detected IK(Ca) channels per patch, a higher IK(Ca) channel NPo, and a greater total patch current than their WKY counterparts. Further analysis revealed a greater Ca2+ sensitivity of SHR than WKY IK(Ca) channels. These results suggest that IK(Ca) channel function is altered in isolated membrane patches of arterial muscle from genetically hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Hyperpolarization of in situ rat saphenous vein in response to axial stretch.

The goal of this study was to measure the effect of axial stretch on vascular smooth muscle (VSM) transmembrane potential (Em) and external diameter (De) of intact and deendothelialized rat saphenous veins (SV). Incremental increases in length of SV were produced in situ by biaxial stretch of its perivascular connective tissue. Em was measured in situ with glass microelectrodes and De with a high-resolution eyepiece or on-line video microangiometer. Vessels were locally denervated by 20 min superfusion with 6-hydroxydopamine. Endothelium was removed by maintaining an air bolus in the lumen for 6 min. Axial stretch of endothelium-intact SV from a baseline length (Lo, at which there was no vessel buckling or folding) to 120% Lo induced a small depolarization from -56 +/- 1.2 to -53 +/- 0.8 mV. This was followed by a substantial hyperpolarization to -65 +/- 1.4 mV at 140% Lo. However, a depolarization was observed in deendothelialized SV from -47 +/- 1.3 mV at Lo to -43 +/- 1.8 mV at 140% Lo. Neither Em response was influenced by local denervation. Relative to Lo, 40% stretch also attenuated norepinephrine-induced vasoconstriction. These results suggest that axial stretch of SV can lead to release of endothelium-derived factor(s) that hyperpolarizes venous VSM and possibly attenuates stretch-induced and adrenergic vasoconstriction. Such a response may act as a protective mechanism to attenuate vasoconstriction induced by axial stretch.

Animals↗
PubMed1993

Altered beta-receptor control of in situ membrane potential in hypertensive rats.

Sympathetic neural activation of vascular smooth muscle beta-receptors induces membrane hyperpolarization and arterial relaxation. This response, which likely is mediated by the Gs protein-adenylyl cyclase-cyclic AMP signaling cascade, is reduced in some hypertensive animal models and in human essential hypertension. Since reduced beta-receptor-mediated vasodilation is a potential mechanism for enhanced arterial resistance, this study was designed to identify which step (or steps) in the beta-receptor signaling cascade is altered in hypertension. Transmembrane potentials were recorded in situ in small first-order arterioles and venules of cremaster muscle from hypertensive, reduced renal mass rats and normotensive, sham-operated controls. Vascular muscle cells in arterioles and venules of hypertensive rats were 5-7 mV more depolarized than in respective vessels of control rats during superfusion with physiological salt solution. Hyperpolarization and depolarization responses were reduced in hypertensive rats during superfusion with a beta-receptor agonist and antagonist, respectively, suggesting attenuated beta-receptor responsiveness compared with normotensive rats. Furthermore, direct activation of Gs protein by 10 ng/mL cholera toxin did not affect arterial or venous transmembrane potential in hypertensive rats, but hyperpolarized arterial and venous vascular muscle in normotensive controls by 17 mV. However, when the Gs protein-adenylate cyclase coupling step of the beta-receptor cascade was bypassed by using 10(-5) M forskolin to directly activate adenylate cyclase, arterial and venous vascular muscle of hypertensive rats hyperpolarized by 25-27 mV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1992

Pressure-induced activation of membrane K+ current in rat saphenous artery.

Pressurization of isolated arteries may result in Ca(2+)-dependent contraction and membrane depolarization. Because the open state probability of some vascular muscle K+ channels is augmented by rises in cytosolic Ca2+ and membrane depolarization, we investigated the possibility that increases in intraluminal pressure activate K+ channels in isolated, perfused rat saphenous arteries. Stepwise increases in intraluminal pressure from 5 to 205 mm Hg resulted in increasing, active arterial contraction, measured as smaller diameters in physiological salt solution than in Ca(2+)-free solution. Addition of 10 mM tetraethylammonium to the physiological salt solution to block arterial muscle K+ channels caused progressively greater diameter reductions at pressures above 25 mm Hg. Microelectrode measurements of membrane potential showed that tetraethylammonium depolarized arterial muscle more at 105 mm Hg (16 +/- 1 mV) than at 25 mm Hg (10 +/- 1 mV). The sensitivity of K+ current to tetraethylammonium was also demonstrated in patch-clamped vascular muscle cells from the same arteries. Peak whole-cell K+ current was suppressed 47% and 79% by 1 and 10 mM tetraethylammonium, respectively. This same current was enhanced 3.6-fold by the Ca2+ ionophore A23187 (10 microM), suggesting a Ca2+ dependence. We conclude that increases in intraluminal pressure progressively activate tetraethylammonium-sensitive K+ channels in the arterial muscle membrane. This can serve as a negative feedback mechanism to limit pressure-induced arterial constriction.

Animals↗
PubMed1991

Sympathetic neural control of vascular muscle in reduced renal mass hypertension.

Vascular smooth muscle (VSM) transmembrane potentials (Em) were measured in situ in small branch arteries (150-300-microns o.d.), small branch veins (300-400-microns o.d.), arterioles (90-150-microns o.d.), and venules (80-250-microns o.d.) in the mesenteric and gracilis muscle and the arterioles and venules of cremaster muscle vascular beds in anesthetized rats with reduced renal mass hypertension (HT-RRM) and normotensive sham-operated RRM control rats. All rats were given a 4% NaCl diet for 2 weeks with water ad libitum. Relative to sham, HT-RRM mesenteric and gracilis arterial and venous vessels, but not the microvessels of the cremaster muscle bed, were less polarized during superfusion with normal physiological salt solution. Also relative to sham, hyperpolarization responses to local sympathetic neural (SNS) denervation with 6-hydroxydopamine were greater in mesenteric and gracilis small arteries, arterioles, veins, and venules but not in cremaster microvessels. The immediate (less than 5-minute) electrogenic depolarization response to local blockade of VSM Na(+)-K+ pump activity with 10(-3) M ouabain was similar between each respective HT-RRM and sham vessel pair in each vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The inhibitory action of halothane on reflex constriction in mesenteric capacitance veins.

Potent inhalational anesthetics depress autonomic reflex responses at multiple sites. Most studies emphasize cardiac chronotropic changes and changes in systemic blood pressure. Recently, active reflex venoconstriction of 500-1,000 microns O.D. mesenteric veins has been demonstrated. In the current study, the effects of halothane on the reflex responses of similar mesenteric veins were measured. Mesenteric vein diameter and intravenous pressure were measured in 500-1,000 microns O.D. veins from the mesentery of segments of terminal ileum externalized in situ from 27 New Zealand white rabbits anesthetized with alpha-chloralose. Mean arterial pressure was measured with femoral arterial cannulation, and heart rate was determined from the arterial pressure signal. In a separate group of six animals, sympathetic efferent nerve activity was measured from a postganglionic splanchnic nerve. Reflex venoconstriction and increases in mean arterial pressure and mesenteric vein pressure in response to bilateral carotid occlusion were attenuated by 0.5% and 1% inhaled halothane but not by superfusate equilibrated with 3% halothane. Decreases in mesenteric vein diameter and increases in mesenteric vein pressure in response to celiac ganglion stimulation were unaffected by both 0.5% inhaled halothane and superfusate equilibrated with 5% halothane. The bilateral carotid occlusion reflex-mediated increase in sympathetic efferent nerve activity was depressed by both 0.5% and 1% inhaled halothane. The effect of inhaled halothane on prestimulation baseline vein diameter was inconsistent. Superfusate equilibrated with 5% but not 3% halothane caused baseline venodilation. These results suggest a mechanism whereby control of venous tone is inhibited by halothane proximal to the postganglionic neuron. This could involve central or ganglionic inhibition.

Animals↗
PubMed1989

Electrical and mechanical responses of rat saphenous vein to short-term pressure load.

The magnitude and mechanism of myogenic response of vascular smooth muscle (SM) in rat distal saphenous vein was assessed from SM membrane potential (Em) measured in situ and in vitro with glass microelectrodes and from active and passive stress and strain calculated from changes in vessel diameter measured in vitro via videomicroscopy. Elevation of intraluminal pressure from 2.2 +/- 0.2 (SE) mmHg (control) to 15 +/- 0.8 mmHg for 1 h in a series of in vitro vessel segments perfused with physiological salt solution at 0.2 ml/min induced a maintained and reversible depolarization of 18 +/- 0.9 mV. A 7.6 +/- 0.4-mmHg pressure increase induced a 12.9 +/- 1.2-mV depolarization in a second series. In a third series, 5-mmHg pressure increments induced significant increments in active isometric stress and isobaric strain. Opening an acute, reversible in situ femoral artery to saphenous vein shunt caused a 4- to 5-mmHg venous pressure elevation, a 10-fold increase in venous blood flow, and a 12.1 +/- 0.9-mV venous SM depolarization. Thus a short-term pressure load causes sustained, reversible venous SM cell depolarization both in vitro and in situ, coupled with active strain and stress generation in the vein wall. These results support our hypothesis that SM of peripheral veins can contribute to an intrinsic capacity autoregulation.

Algorithms↗
PubMed1989

Effect of long-term tilt on mechanical and electrical properties of rat saphenous vein.

Femoral vein pressure in adult male Sprague-Dawley rats kept in specially designed tubelike cages rose immediately from a control value of 2.9 +/- 0.2 (SE) mmHg to a gravity-induced sustained value of 5.9 +/- 0.2 mmHg on initiation of a 2-wk 45 degrees head-up tilt period. Femoral arterial pressure was not altered by tilting. In 2 wk mean external diameter, but not total wall thickness, of in vitro distal saphenous vein segments from tilted rats was increased approximately 30% above that of segments from nontilted controls at each of four successive 5-mmHg intralumenal pressure (IP) increments applied between 0 and 20 mmHg. Consequently, in tilted rats isobaric stress was increased 38% at low and 24% at high IP, whereas incremental distensibility was decreased at mid IP. Vascular smooth muscle (VSM) in tilted rat vein, but not artery, was hyperpolarized relative to controls both in vitro at normal physiological pressures [membrane potential (Em) = -58.2 +/- 0.8 vs. -52.4 +/- 0.8 mV, respectively] and in situ during local neural blockade (Em = -61.3 +/- 2.3 vs. -53.5 +/- 0.5 mV, respectively). The conclusion is that a moderate chronic elevation of IP in a vein results in hyperpolarization of its VSM and an elevation of its total capacity due to an as yet unexplained mechanism of physiological adaptation.

Adaptation, Physiological↗