Rabbit Facial Vein Research Articles

A Structural Model of the Venous Wall Considering Elastin Anisotropy

The three-dimensional biomechanical behavior of the vascular wall is best described by means of strain energy functions. Significant effort has been devoted lately in the development of structure-based models of the vascular wall, which account for the individual contribution of each major structural component (elastin, collagen, and vascular smooth muscle). However, none of the currently proposed structural models succeeded in simultaneously and accurately describing both the pressure-radius and pressure-longitudinal force curves. We have hypothesized that shortcomings of the current models are, in part, due to unaccounted anisotropic properties of elastin. We extended our previously developed biomechanical model to account for elastin anisotropy. The experimental data were obtained from inflation-extension tests on facial veins of five young white New Zealand rabbits. Tests have been carried out under a fully relaxed state of smooth muscle cells for longitudinal stretch ratios ranging from 100% to 130% of the in vivo length. The experimental data (pressure-radius, pressure-force, and zero-stress-state geometries) provided a complete biaxial mechanical characterization of rabbit facial vein and served as the basis for validating the applicability and accuracy of the new biomechanical model of the venous wall. When only the pressure-radius curves were fitted, both the anisotropic and the isotropic models gave excellent results. However, when both pressure-radius and pressure-force curves are simultaneously fitted, the model with isotropic elastin shows an average weighted residual sum of squares of 8.94 and 23.9 in the outer radius and axial force, respectively, as compared to averages of 6.07 and 4.00, when anisotropic elastin is considered. Both the Alkaike information criterion and Schwartz criterion show that the model with the anisotropic elastin is more successful in predicting the data for a wide range of longitudinal stretch ratios. We conclude that anisotropic description of elastin is required for a full 3D characterization of the biomechanics of the venous wall.

Involvement of RhoA/Rho Kinase Pathway in Myogenic Tone in the Rabbit Facial Vein

Myogenic tone (MT), a fundamental stretch-sensitive vasoconstrictor property of resistance arteries and veins, is a key determinant of local blood flow regulation. We evaluated the pathways involved in MT development. The role of the RhoA/Rho kinase, p38 MAP kinase, and HSP27 in MT was investigated in the rabbit facial vein (RFV), previously shown to possess MT at a pressure level equivalent to 20 mm Hg. Venous MT is poorly understood, although venous diseases affect a large proportion of the population. Stretched RFV are characterized by a temperature-sensitive MT, which is normal at 39 degrees C but fails to develop at 33 degrees C. This allows for the discrimination of the pathways involved in MT from the multiple pathways activated by stretch. Isolated RFV segments were mounted in organ baths and stretched. Temperature was then set at 33 degrees C or 39 degrees C. MT was associated to the translocation of RhoA to the plasma membrane and the Rho kinase inhibitor Y27632 decreased stretch-induced MT by 93.1+/-4.9%. MT was also associated to an increase in p38 (131.0+/-12.5% at 39 degrees C versus 100% at 33 degrees C) and HSP27 phosphorylation (196.1+/-13.3% versus 100%), and the p38 MAP kinase inhibitor SB203580 decreased MT by 36.5+/-8.1%. (39 degrees C, compared with RFV stretched at 33 degrees C). Finally, phosphorylation of p38 was blocked by Y27632 and HSP27 phosphorylation was inhibited by SB203580 and Y27632. Thus, MT and the associated p38 and HSP27 phosphorylation seem to depend on RhoA/Rho kinase activation in stretch RFV.

Pharmacological evidence that tetraethylammonium-sensitive, iberiotoxin-insensitive K+ channels function as a negative feedback element for sympathetic neurotransmission by suppressing ω-conotoxin-GVIA-insensitive Ca2+ channels in the relaxation of rabbit facial vein

Pharmacological evidence that tetraethylammonium-sensitive, iberiotoxin-insensitive K+ channels function as a negative feedback element for sympathetic neurotransmission by suppressing ω-conotoxin-GVIA-insensitive Ca2+ channels in the relaxation of rabbit facial vein

Pharmacological evidence that tetraethylammonium-sensitive, iberiotoxin-insensitive K+ channels function as a negative feedback element for sympathetic neurotransmission by suppressing omega-conotoxin-GVIA-insensitive Ca2+ channels in the relaxation of rabbit facial vein.

The facial vein isolated from various species relaxes in response to electrical field stimulation (EFS). EFS-elicited relaxation of the facial vein is mediated through the release of noradrenaline (NA) from sympathetic nerve endings and the subsequent activation of smooth muscle beta-adrenoceptors. The release of NA from sympathetic nerve endings in arterial tissues requires transmembrane Ca2+ influx, mediated predominantly by voltage-gated N-type Ca2+ channels. The present pharmaco-mechanical study was undertaken to determine whether the N-type channel is the exclusive pre-junctional Ca2+ channel mediating NA release from sympathetic nerve endings in the rabbit facial vein. Possible roles of K+ channels in the sympathetic neurotransmission were also examined, especially focusing on the contribution of voltage-dependent, Ca2+-activated K+ (BKCa) channels. An isolated ring preparation of the rabbit facial vein exhibited intrinsic myogenic tone which lasted for several hours when stretched. EFS produced frequency-dependent (0.25-2 Hz) relaxation in this preparation. EFS-elicited relaxation was abolished by tetrodotoxin (TTX, 1 microM), guanethidine (5 microM) or propranolol (1 microM), indicating that NA released from sympathetic nerve endings was mediating the relaxant response. NA-mediated neurogenic relaxation was almost eliminated by omega-conotoxin-GVIA (1 microM), an N-type Ca2+ channel blocker. On the other hand, tetraethylammonium (TEA, 2 mM) strongly potentiated EFS-elicited relaxation without affecting the relaxation induced by exogenously applied NA. This potentiation by TEA was not profoundly diminished by omega-conotoxin-GVIA (1 microM) alone or omega-conotoxin-GVIA (1 microM) plus omega-agatoxin IVA (10 nM, P-type channel blocker), but was almost abolished by omega-conotoxin-GVIA (1 microM) plus omega-agatoxin IVA (10 nM) plus omega-conotoxin-MVIIC (3 microM, N-, P- and Q-type channel blocker). The potentiating effect of TEA was not mimicked by iberiotoxin (100 nM) or charybdotoxin (3 microM), both of which block BKCa channels. These findings suggest that pre-junctional N-type Ca2+ channels play the predominant role in the sympathetic nerve transmission in the rabbit facial vein, as in peripheral arterial vascular beds. In addition, Ca2+ channels resistant to 1 microM omega-conotoxin-GVIA, most probably Q-type channels, appear to be present at the sympathetic nerve endings in the rabbit facial vein and contribute substantially to the regulation of NA release from the nerve endings. Prejunctional K+ channels, sensitive to TEA but pharmacologically distinct from iberiotoxin-sensitive BKCa channels, seem to be functionally coupled intimately with the omega-conotoxin-GVIA-resistant Ca2+ channels, and thus function as a negative feedback element in sympathetic neurotransmission in the rabbit facial vein.

Potentiation of stretch-induced tone in the rabbit facial vein by an isoquinoline derivative, LOE 908.

The rabbit facial vein exhibits extracellular Ca2+- and temperature-dependent spontaneous myogenic tone in response to stretch. The present study aimed to elucidate pharmacological characteristics of Ca2+ entry mechanisms responsible for the stretch-induced tension development of the rabbit facial vein. Ca2+- and temperature-sensitive vascular tone in response to stretch was refractory to L-type Ca2+ channel blockers such as nifedipine and diltiazem but was abolished by papaverine or SK&F 96365 which blocks both receptor- and store-operated Ca2+ channels. Interestingly, LOE 908, another type of voltage-independent Ca2+-permeable channel blocker, showed augmentation of the stretch-induced vascular tone instead of inhibition. Potentiation by LOE 908 of stretch-induced vascular tone was also extracellular Ca2+-dependent and counteracted by SK&F 96365. Membrane stretch-activated Ca2+ channels in the rabbit facial vein smooth muscle cells may have a unique characteristic that their opening is stimulated by LOE 908 and thus is distinguishable from other voltage-independent Ca2+-permeable channels.

Potentiation of stretch-induced tone in the rabbit facial vein by an isoquinoline derivative LOE 908

Potentiation of stretch-induced tone in the rabbit facial vein by an isoquinoline derivative LOE 908

Stretch induces mitogen-activated protein kinase activation and myogenic tone through 2 distinct pathways.

The aim of this study was to evaluate the involvement of the mitogen-activated protein kinase (ERK1/2) pathway in response to stretch in a blood vessel developing myogenic tone on stretch. Indeed, in resistance arteries and veins, the main effect of pressure is to induce a maintained vasoconstrictor (myogenic) tone. Isolated segments of rabbit facial vein were mounted in organ baths and submitted to isometric stretch. In this experimental model, myogenic tone was absent when the bath temperature was 33 degrees C. ERK1/2 activity was determined in each isolated segment by an in-gel kinase assay. Wall tension and ERK1/2 activity were measured in the same samples in the presence (39 degrees C) or in the absence of myogenic tone (33 degrees C). At 39 degrees C, a 5-mN wall tension induced myogenic tone (5.7+/-1.8 mN) and an increase in ERK1/2 activity (282+/-52% versus unstretched vessels, P<0.05). At 33 degrees C, in the absence of myogenic tone, ERK1/2 activity was similarly increased by stretch (254+/-35% versus unstretched vessels). The calcium-dependent and -independent protein kinase C (PKC) blocker Ro-31-8220 (5 x 10(-7) mol/L), but not the calcium-dependent PKC blocker Go-6976 (10(-6) mol/L), inhibited myogenic tone. However, ERK1/2 activity was not affected by either PKC blocker. Genistein (10(-7) mol/L), a general tyrosine kinase inhibitor, but not herbimycin A (5 x 10(-7) mol/L), a cSrc-family tyrosine kinase inhibitor, suppressed stretch-induced ERK1/2 activation (P<0.05) without affecting myogenic tone. Nifedipine (10(-6) mol/L), a voltage-dependent calcium entry inhibitor, and ryanodine (10(-6) mol/L), which depletes calcium stores, both inhibited ERK1/2 activity (113+/-12% and 121+/-7%, respectively; P<0. 05) without affecting myogenic tone. The mitogen-activated protein kinase kinase inhibitor PD 98059 (5 x 10(-6) mol/L) also inhibited ERK1/2 activation without affecting myogenic tone. The present results suggest that stretching the rabbit facial vein induced 2 distinct pathways, one leading to myogenic tone (via a non-calcium-dependent PKC activation) and one leading to ERK1/2 activation through a calcium-dependent pathway involving tyrosine kinase.

Sarcoplasmic reticulum and endothelium independently regulate venous smooth muscle [Ca(2+)](i) and contraction.

In rings of rabbit facial vein (RFV), depletion of sarcoplasmic reticulum (SR) Ca(2+) by caffeine abolished the subsequent isometric contraction to 25 mM K(+) physiological salt solution (25K-PSS). However, the associated steady-state increase of smooth muscle intracellular free Ca(2+) concentration ([Ca(2+)](i)), measured using fura PE3 and cuvette photometry, was not altered. Treatment with the specific SR Ca(2+) pump inhibitor cyclopiazonic acid (30 microM) after caffeine-induced SR Ca(2+) depletion restored and greatly augmented the 25K-PSS-induced contraction. This suggests that SR Ca(2+) depletion leads to a dissociation of K(+)-induced [Ca(2+)](i) increase from contraction that was dependent on Ca(2+) pump-mediated SR Ca(2+) uptake. Endothelium removal augmented the 25K-PSS-induced [Ca(2+)](i) increase after caffeine-induced SR Ca(2+) depletion. However, this was associated with only a small and transient contraction. Exposure of endothelium-denuded RFV to cyclopiazonic acid after caffeine-induced SR Ca(2+) depletion further amplified the 25K-PSS-induced [Ca(2+)](i) increase, which was associated with a large and sustained contraction. However, the latter [Ca(2+)](i) increase was still higher than in endothelium-intact RFV. This suggests that the endothelium dampens the [Ca(2+)](i) rise associated with K(+)-induced Ca(2+) influx, but independently of Ca(2+) pump-mediated SR Ca(2+) uptake.

Barium and 4-Aminopyridine Inhibit Flow-Initiated Endothelium-Independent Relaxation

Although much is known about the underlying mechanism of endothelium-dependent flow-induced vasorelaxation, the cellular processes responsible for the endothelium-independent flow-induced relaxation observed in some vessels is unknown. As there is evidence for the participation of K⁺ channels in the endothelium-dependent response, the present study was designed to determine whether such channels are involved in the endothelium-independent response and if so, which ones. We examined the effects of various selective K⁺ channel blockers on endothelium-independent relaxation initiated by intraluminal flow (10–80 µl/min), and by an endothelium-independent vasodilator sodium nitroprusside (SNP, 1 nmol/l to 3 µmol/l) in segments of the rabbit facial vein under isometric conditions. Flow-initiated relaxation was abolished by 25 and 40 mmol/l K⁺ as well as 10 mmol/l tetraethylammonium (TEA), significantly inhibited by 100 µmol/l Ba²⁺, 5 mmol/l Cs⁺ and 7.5 mmol/l 4-aminopyridine (4-AP), but unaffected by 5 µmol/l glibenclamide and 50 nmol/l charybdotoxin. Relaxation induced by SNP was reduced by 7.5 mmol/l 4-AP, but not by any of the above drugs in their listed concentrations. The inhibitory effect of 100 µmol/l Ba²⁺ on the relaxation caused by low concentrations of K⁺ (15–20 mmol/l) supports the presence of inward rectifier K⁺ channels in the vascular smooth muscle cells of this tissue. We speculate that endothelium-independent flow-initiated relaxation of the rabbit facial vein may be associated with activation of inward rectifier and voltage-dependent K⁺ channels. The latter may also contribute to the vasorelaxation initiated by SNP.

Endothelium-independent relaxant effect of 5-hydroxytryptamine (5-HT) on the isolated rabbit facial vein.

The facial vein in several species has been shown to have unusual properties, including exhibition of spontaneous myogenic tone and relaxation to norepinephrine (NE). The present study was undertaken to characterize the relaxant effect of 5-hydroxytryptamine (5-HT) on the rabbit facial vein. An isolated ring preparation of the rabbit facial vein exhibited intrinsic tone when it was stretched and the spontaneous contraction continued for hours. 5-HT concentration-dependently relaxed facial veins exhibiting spontaneous contraction. The relaxation was not inhibited by rubbing the endothelium or by NG-nitro-L-arginine (10(-4) M), a nitric oxide (NO) synthase inhibitor. The 5-HT-induced relaxation was also unaffected by pretreatment with indomethacin (10(-5) M), a cyclooxygenase inhibitor, and propranolol (10(-6) M), a both beta-adrenoceptor and 5-HT18-receptor antagonist. In contrast, 5-HT-induced relaxation of the facial vein was concentration-dependently antagonized by methysergide (10(-7) M and 10(-6) M), a non-selective 5-HT1- and 5-HT2-receptor antagonist, but not by NAN-190 (10(-6) M) and SDZ-205,557 (10(-6) M), antagonists for 5-HT1A- and 5-HT4-receptors, respectively. A higher (10(-6) M), but not lower (3 x 10(-7) M) concentration of ketanserin, a 5-HT2-receptor antagonist, slightly inhibited the 5-HT-induced relaxation. These results indicate that 5-HT-induced relaxation is not due to indirect mechanisms mediated by NE released from the sympathetic nerve terminals, or by endogenous prostanoid and endothelium-derived relaxing factor (EDRF = NO) released from the vascular tissues, but due to a direct effect on the 5-HT receptors located on vascular smooth muscle cells. However, the subtype of 5-HT receptor that produces relaxation of the rabbit facial vein remains to be clarified.

Small changes in extracellular sodium influence myogenic tone in rabbit facial vein by changing its sensitivity to calcium.

Extracellular Na+ concentration ([Na+]e) significantly effects the regulation of myogenic tone in isolated blood vessels. We examined the effect of small changes in [Na+]e on simultaneous changes in stretch-activated myogenic tone in rabbit facial vein and 45Ca2+ unidirectional influx and net uptake. Decreasing [Na+]e from 150 to 120 mmol/l augmented myogenic tone (control: 3.15 +/- 0.27 mN, n = 22) by 89 +/- 29%, while raising [Na+]e to 165 mmol/l attenuated myogenic tone to 80 +/- 2% of control. Changes in myogenic tone induced by alterations in [Na+]e were not accompanied by proportional changes in 45Ca2+ net uptake. 45Ca2+ unidirectional influx per unit of wall force (10.2 +/- 1.0 pmol/mg per mN force, n = 22, control) was decreased to 6.1 +/- 0.6 pmol/mg per mN (n = 20, P < 0.05) and increased to 21.0 +/- 2.5 pmol/mg per mN (n = 14, P < 0.05) when [Na+]e was 120 or 165 mmol/l, respectively, suggesting that decreasing [Na+]e is related to an increased sensitivity to calcium. We conclude that, in the rabbit facial vein, the sensitivity of myogenic tone to changes in [Na+]e may reflect changes in the sensitivity of smooth muscle to Ca2+ through a change in mechanoreceptor sensitivity.

Intracellular Ca 2+ Release in Flow-Induced Contraction of Venous Smooth Muscle

We designed the present study to determine whether Ca2+ release from intracellular stores contributes to flow-induced contraction. We carried out experiments on segments of rabbit facial vein under isometric conditions. Intraluminal flow by perfusion of physiological salt solution (10 to 80 microL/min) caused contraction in this vessel, which was significantly inhibited by (1) 30-minute pretreatment with 10 mumol/L ryanodine, the sarcoplasmic reticulum Ca2+ channel opener, and (2) 30-minute pretreatment with concomitant application of 20 mmol/L caffeine and 1 mumol/L cyclopiazonic acid in Ca(2+)-free medium to deplete the sarcoplasmic reticulum. In comparison, contraction initiated by 300 nmol/L histamine was significantly attenuated by the same interventions. K+ (25 mmol/L)-induced contraction was unaffected by ryanodine but was reduced after depletion of the sarcoplasmic reticulum. The phospholipase C inhibitor 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (10 mumol/L) inhibited contractions induced by flow and histamine but not by K+. These findings indicate that Ca2+ release from intracellular stores, presumably via the phosphatidylinositol pathway, contributes to flow- and histamine- but not raised K(+)-induced contractions in this vessel.

Magnitude of flow-induced contraction and associated calcium influx in the rabbit facial vein is dependent upon the level of extracellular sodium.

Intraluminal flow can cause both dilation or constriction of small arteries, depending on the level of tone. Both responses are specifically modulated in the same way by small changes in extracellular Na+ ([Na+]e). We have investigated the effect of changes in [Na+]e on the level of contraction induced by a standard flow of physiological salt solution in ring of segments of the rabbit facial vein and on the associated 45Ca2+ influx and net uptake. Decreasing [Na+]e by 20% reduced the response to flow by 58%, and increasing it by 20% augmented the flow response by the same extent. There is a linear relationship between the level of the flow-induced contraction and [Na+]e over the range 120-180 mM. An alteration in [Na+]e of 10 mM corresponds to a 20% change in flow-induced contraction. This relationship is quantitatively the same as that previously reported for the rabbit ear resistance artery [10]. Histamine (1 microM)-induced tone was not affected by changes in [Na+]e within the range 75-180 mM. 45Ca2+ influx and net uptake per unit force developed in response to flow were unaffected by these changes in [Na+]e. The flow-induced contraction of the vein was selectively, in comparison to that due to histamine, attenuated by amiloride, methyl-isobutyl-amiloride and monensin. It is argued that the observation that flow-induced contraction, caused by small alterations in extracellular sodium concentration, is not associated with changes in calcium uptake per unit force is consistent with an extracellular flow sensor.(ABSTRACT TRUNCATED AT 250 WORDS)

Phorbol Ester-induced Potentiation of Myogenic Tone is not Associated with Increases in Ca 2+ Influx, Myoplasmic Free Ca 2+ Concentration, or 20-kDa Myosin Light Chain Phosphorylation

We studied the extent of Ca 2+ influx, myoplasmic free Ca 2+ concentration changes, and phosphorylation of the regulatory 20-Kda myosin light chain (LC 20) associated with the potentiation of stretch-induced myogenic tone in the rabbit facial vein. The protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), was used to augment Ca 2+-dependent stretch-induced myogenic tone. Veins stretched to an optimal resting tension in physiological salt solution (PSS) containing 0.4 mM of Ca 2+ developed stretch-induced myogenic tone. Tissues incubated in Ca 2+-free PSS, either with or without PMA (0.1 μM) did not develop myogenic tone. Readmission of Ca 2+ (0.4 mM) caused three-fold increase in the contraction in PMA-treated segments (710 ± 60 mg, n = 29 v control: 188 ± 10 mg, n = 24). This increased contraction was not associated with additional increases in either Ca 2+ influx (73.5 ± 6.9 pmol/mg of tissue/min, n = 29 v control: 61.1 ± 5.7 pmol/mg of tissue/min, n = 24), myoplasmic free Ca 2+ concentration of LC 20, (0.44 ± 0.02 mol PO 4/mg LC 20, n = 9 v control: 0.43 ± 0.03 mol PO 4/mol LC 20, n = 7). Our results suggest that PKC activation amplifies stretch-induced myogenic tone in the rabbit facial vein through target proteins that are not associated with regulation of Ca 2+ influx, myoplasmic free Ca 2+ concentration, or LC 20 phosphorylation. We conclude that the PKC-mediated potentiation of stretch-induced myogenic tone is due to an increased sensitivity of the contractile apparatus to Ca 2+.

Myogenic tone of rabbit facial vein and posterior cerebral artery is influenced by changes in extracellular sodium.

We examined the effect of small changes in extracellular Na+ concentration ([Na+]e) on myogenic tone (MT) in isometrically mounted ring segments of the rabbit facial vein and in pressurized cannulated posterior cerebral artery segments. Decreasing [Na+]e from 150 to 120 mM in the vein increased MT by 24%, and raising [Na+]e to 165 mM attenuated it by 30%. In pressurized posterior cerebral arteries, decreasing [Na+]e to 120 mM reduced the intraluminal diameter by 12%, whereas increasing [Na+]e to 165 mM increased it by 17%. MT was inhibited by amiloride [50% inhibitory concentration (IC50) = 17 +/- 6 microM], an inhibitor of Na(+)-H+ exchange. Diisothiocyanatostilbene sulfonic acid, a Na(+)-Cl(-)-HCO3- cotransporter blocker, inhibited MT with an IC50 of 4.4 +/- 0.65 microM. Ouabain increased MT [50% effective concentration (EC50) = 0.10 +/- 0.04 microM] as did the reintroduction of HCO3- (EC50 5.0 +/- 1.5 mM). Our study suggests that MT in the rabbit posterior cerebral artery and rabbit facial vein is modulated by changes in [Na+]e. This effect is independent of the method used to register changes in wall force. The sensitivity of the tone to changes in [Na+]e and the independence of vessel diameter at different pressures at various [Na+]e may reflect changes in the sensitivity of smooth muscle stretch or mechanoreceptors to [Na+]e.

O-302 - Relaxant effect of 5-hydroxytryptamine (5-HT) on the isolated rabbit facial vein.

O-302 - Relaxant effect of 5-hydroxytryptamine (5-HT) on the isolated rabbit facial vein.

Influence of impulse pattern on noradrenaline release from sympathetic nerves in cerebral and some peripheral vessels.

Earlier findings suggested that the physiological firing rate in sympathetic nerves did not exceed 10 Hz. Later recordings have revealed that this is a net value: impulses are usually not continuous but occur in bursts of high frequencies separated by quiet periods. The effects of continuous and burst-like neurogenic activation in various isolated blood vessels were compared. In the first part of the study changes in vascular tone were registered. Electrical field stimulatory parameters were chosen to give tetrodotoxin-blockable, neurogenic responses. From dose-response experiments in rat caudal artery a net frequency of 6 Hz was chosen, for bursts usually designed as 30 Hz during 0.2 s followed by a quiet period of 0.8 s. In the rabbit ear artery the neurogenic contraction was enhanced by a mean of near 50% during stimulation with bursts. Now appeared a minor phentolamine-resistant portion, which was not due to release of NPY, 5-HT, histamine or ATP. Also in the rat caudal artery and monkey pial artery a significant enhancement of contraction was seen during burst simulation, whereas in the rabbit facial vein no significant difference in dilatation through beta-receptor activation was obtained. In vessels that do not normally respond with purely neurogenic contractions/dilatations during continuous stimulation, like pial arteries from the rat and rabbit, not even bursts revealed a neurogenic response. In a second series of experiments the influence of continuous and burst-like nerve activation on the release of [14C]noradrenaline was studied in monkey, rabbit and rat pial arteries, rat caudal artery and rabbit central ear artery and facial vein.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of inhibitory noradrenergic transmission in the rabbit facial vein

In isolated buccal segment of the rabbit facial vein, electrical responses produced by perivascular nerve stimulation and exogenously applied noradrenaline (NA) were recorded from the smooth muscle cells using microelectrode. Perivascular nerve stimulation hyperpolarized the smooth muscle cell membrane. The hyperpolarization was converted to depolarization after application of the beta-adrenoceptor antagonist, propranolol, and the depolarization was blocked by alpha 2-adrenoceptor antagonists, yohimbine. These responses elicited by nerve stimulation were blocked by tetrodotoxin or guanethidine, but not by atropine. Exogenously applied NA mimicked the responses elicited by nerve stimulation. The amplitude of the beta-adrenoceptor-mediated hyperpolarization was increased in low potassium solution, decreased in high potassium solution, but unaltered by low sodium or low chloride solution, i.e., the hyperpolarization may be generated by an increase in potassium conductance of the membrane. An involvement of the apamin-sensitive (Ca-dependent) potassium channel or sodium-potassium ATPase in the hyperpolarization was ruled out.

Staurosporine, a protein kinase C inhibitor, attenuates Ca 2+-dependent stretch-induced vascular tone

The effects of protein kinase C inhibition by staurosporine was studied on Ca-dependent tone of the rabbit facial vein. Tone was produced either by stretch or by readmission of Ca2+ in a non-depolarizing Ca2+-free salt solution. Stretch-induced tone was inhibited by staurosporine. When tissues were incubated in a Ca2+-free solution, staurosporine (50 nM) inhibited the contractile responses produced by readmission of Ca2+. These observations suggest that maintenance of stretch-induced extracellular Ca2+-dependent tone may be regulated by protein kinase C.

Stretch-dependent calcium uptake associated with myogenic tone in rabbit facial vein.

Many blood vessels possess stretch-dependent myogenic tone. This tone contributes to the active resistance in small arteries, which regulates blood flow in the body. In this report we describe results indicating that stretch-dependent myogenic tone in the rabbit facial vein, a vascular preparation with useful experimental properties, is accompanied by an increased uptake of 45Ca2+. This influx may not occur through voltage-gated Ca2+ channels, since neither the extent of myogenic tone nor 45Ca2+ influx is affected by a concentration of 1,4-dihydropyridine (PN 200-110, 10 nM) that reduces tone and 45Ca2+ influx due to the depolarization by K+. These results indicate that in myogenically active vessels a stretch-activated influx of Ca2+ may occur through distinct Ca2+-entry pathways.