NA-induced Depolarization Research Articles

Na+-independent, nifedipine-resistant rat afferent arteriolar Ca2+ responses to noradrenaline: possible role of TRPC channels

In rat afferent arterioles we investigated the role of Na(+) entry in noradrenaline (NA)-induced depolarization and voltage-dependent Ca(2+) entry together with the importance of the transient receptor potential channel (TRPC) subfamily for non-voltage-dependent Ca(2+) entry. R (340/380) Fura-2 fluorescence was used as an index for intracellular free Ca(2+) concentration ([Ca(2+)](i)). Immunofluorescence detected the expression of TRPC channels. TRPC 1, 3 and 6 were expressed in afferent arteriolar vascular smooth muscle cells. Under extracellular Na(+)-free (0 Na) conditions, the plateau response to NA was 115% of the baseline R(340/380) (control response 123%). However, as the R(340/380) baseline increased (7%) after 0 Na the plateau reached the same level as during control conditions. Similar responses were obtained after blockade of the Na(+)/Ca(2+) exchanger. The L-type blocker nifedipine reduced the plateau response to NA both under control (from 134% to 116% of baseline) and 0 Na conditions (from 112% to 103% of baseline). In the presence of nifedipine, the putative TRPC channel blockers SKF 96365 (30 μm) and Gd(3+) (100 μm) further reduced the plateau Ca(2+) responses to NA (from 117% to 102% and from 117% to 110% respectively). We found that Na(+) is not crucial for the NA-induced depolarization that mediates Ca(2+) entry via L-type channels. In addition, the results are consistent with the idea that TRPC1/3/6 Ca(2+) -permeable cation channels expressed in afferent arteriolar smooth muscle cells mediate Ca(2+) entry during NA stimulation.

Induction of noradrenergic supersensitivity following cordotomy in neonatal rat spinal motoneurons

Patients with spinal cord lesions frequently show autonomic hyperreflexia. The mechanism of autonomic hyperreflexia has been thought to be an acute general autonomic overactivity in response to cutaneous or visceral stimuli, but it remains uncertain. Several kinds of experiments suggest that amplified spinal sympathetic reflexes in the decentralized cord are attributable to the denervation supersensitivity of denervated neurons, which is a well-known phenomenon in denervated muscle fibers. In the present study, changes in the supersensitivity of motoneurons after cordotomy were studied in the spinal cord of neonatal rats. Responses to bath-applied noradrenaline (NA) were recorded from a ventral root of the isolated spinal cord of 6-day-old rats. In normal spinal cords, NA induced depolarization in motoneurons dose-dependently. alpha 1-antagonist prazosin (3 microM) inhibited the deporalization induced by NA, and alpha 2-antagonist rauwolscine (1 microM) potentiated it. In one group of rats, cordotomy was performed 4 days after birth by complete transection of the spinal cord at vertebrate 8th-10th thoracic level, and NA response was examined two days later (when they were 6 days old). In cordotomized rats, NA-induced depolarization was increased with respect to both amplitude and duration. alpha 1- as well as alpha 2-antagonists inhibited the NA response in the spinalized rats. Especially, both antagonists shortened the duration of NA response as compared to normal level. It is concluded that the denervation supersensitivity to NA appears 2 days after cordotomy in the spinal motoneurons of neonatal rats and that the supersensitivity to NA is attributable to the upregulation of both alpha 1- and alpha 2-adrenoceptors on the motoneurons, indicating that a new type of alpha 2-adrenoceptor function appears.

Inhibitory actions of MCI-154 on guinea-pig femoral artery and vein preparations

In guinea-pig femoral artery and vein preparations, the effects of MCI-154 were investigated on: (1) membrane depolarizations produced by 29.6 mM [K+]0 (high-K) solution and noradrenaline (NA) and on e.j.p.s produced by perivascular nerve stimulation; (2) contractions produced by NA, high-K and perivascular nerve stimulation; and, (3) endothelium-dependent relaxation produced by acetylcholine (ACh). In both femoral artery and vein preparations, MCI-154 (up to 10−5 M) did not change the resting membrane potential or the depolarization produced by high-K. In preparations of femoral vein but not femoral artery, MCI-154 reduced NA-induced depolarization. The contractions produced by NA and high-K were reduced by MCI-154, the former more than the latter. The actions of MCI-154 were more pronounced in the vein than in the artery. The excitatory junction potential and contractions produced by perivascular nerve stimulation in guinea-pig saphenous artery preparations were inhibited by MCI-154 (> 10−7 M). ACh-induced relaxations of guinea-pig femoral artery preparations precontracted with high-K were not affected by MCI-154. It was concluded that MCI-154 is an antagonist at postjunctional α2-adrenoceptors, and, at high concentrations, inhibits voltage-dependent Ca2+ influx in vascular smooth muscle cells. These actions may contribute to the hypotensive effect of this drug.

Bunazosin, an α1-adrenoceptor blocker, differentially releases co-transmitters in dog mesenteric vessels

The effects of bunazosin on the electrical and mechanical responses of smooth muscle cells elicited by exogenously applied noradrenaline (NA) and by perivascular nerve stimulation were studied in the isolated mesenteric artery and vein of the dog. NA (above 10 −7 M in the artery and above 3 × 10 −8 M in the vein) depolarized the membrane. Perivascular nerve stimulation evoked an excitatory junction potential (e.j.p.) and slow depolarization in both vessels. Bunazosin and prazosin inhibited the NA-induced depolarization and slow depolarization in the artery but not in the vein. The NA actions in the vein were inhibited by yohimbine. Bunazosin (above 10 −6 M) increased the amplitude of the e.j.p. but decreased the outflow of NA during nerve stimulation. The amplitude and conduction velocity of the compound action potential of perivascular nerves were inhibited by higher concentrations of bunazosin (above 10 −5 M). The results provide evidence that bunazosin has selective inhibitory actions at α 1-adrenoceptors. This drug exerted differential effects on the release of co-transmitters which generate the e.j.p. and the slow depolarization, as bunazosin increased the former and decreased the latter. This suggests that e.j.p. is generated by a substance other than NA.

Electrical and mechanical properties of the capsular smooth muscles of the rabbit prostate in relation to the actions of the alpha 1-adrenoceptor blocker, YM-12617.

1. Electrical and mechanical properties of smooth muscle cells of the rabbit prostate capsule and the actions of the alpha 1-adrenoceptor blocker, YM-12617, were investigated using microelectrode and isometric tension recording methods. 2. The capsular muscles comprised thick and thin muscle bundles. In the former, noradrenaline (NA; 0.1-10 microM) provoked the phasic and tonic mechanical responses, with twitch contractions superimposed on the tonic response. YM-12617, in concentrations over 1 nM inhibited the contraction evoked by any given concentration of NA. Yohimbine (up to 10 microM) slightly inhibited the NA-induced contraction whilst clonidine (up to 10 microM) and acetylcholine (ACh; up to 10 microM) produced no mechanical response. 3. In thin muscle bundles, NA (0.1-10 microM) produced a contraction but the phasic response was small and the tonic response was negligible. These changes were blocked by YM-12617. In contrast, ACh (0.1-10 microM) produced atropine-sensitive, large phasic and tonic responses similar to those observed on application of NA to thick muscle bundles. 4. In thin and thick muscle bundles, the mean resting membrane potentials were -54 and -56 mV, respectively, values which were not statistically different. However, in thick muscle bundles, NA (over 0.1 microM) depolarized the membrane in a concentration-dependent manner and produced repetitive spike generation; ACh (up to 1 microM) did not modify the membrane potential. In thin muscle bundles, the above concentrations of NA hyperpolarized the membrane but ACh produced a large depolarization with repetitive spike generation. 5. In thick muscle bundles, nifedipine (0.3 microM) blocked twitch contractions generated spontaneously or provoked by application of NA with no effect on phasic and tonic responses. The NA-induced depolarization persisted after superfusion with nifedipine up to a concentration of 1.0 microM. In a Ca-free solution containing 2 mM EGTA, NA produced only the phasic responses, and re-addition of Ca (2.6 mM) restored the generation of a tonic response. 6. After application of 0.3 microM nifedipine, the effects of YM-12617 and prazosin were observed on the tonic component of the NA-induced contraction of thick muscle bundles. The ID50 values for YM-12617 and prazosin were 1 nM and 15 nM, respectively (n = 4). YM-12617 shifted the NA concentration-response curve to the right in a concentration-dependent and parallel manner. The Schild plot yielded a straight line with slope of 0.97 +/- 0.05, (n = 4). The pA2 value for YM-12617 was 10.4 +/- 0.05, (n = 4). 7. In thiqk muscle bundles, the depolarization induced by NA (1O microM) was blocked by YM-12617 (over 1 nM) to a greater extent than by prazosin (0.1 microM). Half-inhibition of the NA (10 microM)-induced maximum depolarization by YM-12617 or prazosin occurred at concentrations of 2 nm and 100 nM, respectively. 8. From these mechanical and electrical responses, the heterogeneous nature and distribution of alpha-adrenoceptors and muscarinic receptors has been elucidated in capsular smooth muscles in the rabbit prostate. In both thick and thin muscle bundles, NA-induced electrical and mechanical responses were more potently inhibited by YM-12617 than by prazosin.

<b>EFFECTS OF α-ADRENOCEPTOR ANTAGONISTS AND α,β-METHYLENE ATP ON ELECTRICAL RESPONSES PRODUCED BY NEUROTRANSMITTERS IN SMOOTH MUSCLE CELLS OF THE RAT TAIL ARTERY</b>

Effects of α-adrenoceptor antagonists and α,β-methylene ATP (mATP) on electrical responses elicited by perivascular nerve stimulation were studied in smooth muscle cells of the rat tail artery, and the results were compared with those of exogenously applied noradrenaline (NA) or ATP. Nerve stimulation elicited an excitatory junction potential (e.j.p.) and slow depolarization. The latter component and NA-induced depolarization were blocked by α-adrenoceptor antagonists; prazosin and phentolamine were more potent than yohimbine. The membrane resistance was increased during the slow depolarization and the NA-induced depolarization. mATP depolarized the membrane, decreased the membrane resistance, reduced the time constant of the falling phase of the e.j.p., inhibited the amplitude of the e.j.p. and the ATP-induced depolarization to a similar extent, and enhanced amplitude of the slow depolarization and the NA-induced depolarization. The results provided evidence that in this artery, both α1- and α2-adrenoceptors are involved in the NA-induced depolarization. Inhibition by mATP of the e.j.p. cannot be concluded solely due to desensitization of the postjunctional ATP-receptor.

Electrogenic Na/HCO3 cotransport across basolateral membrane of isolated perfused Necturus proximal tubule.

This study was undertaken to determine whether the proximal tubule of the mud puppy Necturus maculosus possesses a basolateral Na/HCO3 cotransporter. We examined the effects on basolateral membrane potential (Vbl) and intracellular pH (pHi) of 1) lowering basolateral [HCO3-] at constant PCO2, and 2) replacing Na+ with N-methyl-D-glucamine. Vbl and pHi were measured with Ling-Gerard and liquid-membrane pH microelectrodes, respectively, in isolated tubules perfused in vitro. We found that decreasing basolateral [HCO3-] from 10 mM (pH 7.5) to 2 mM (pH 6.8) resulted in an immediate depolarization of 14.9 mV, and a pHi decrease of 0.35. SITS (4-acetamido-4'-isothiocyanostibene-2,2'-disulfonic acid, 0.5 mM) inhibited the HCO3-induced depolarization by 87% and inhibited the initial rate of the pHi decrease by 79%. Replacement of basolateral Na+ with N-methyl-D-glucamine resulted in an immediate depolarization of 11.3 mV, and a pHi decrease of 0.36. SITS inhibited the zero Na-induced depolarization by 86% and the initial rate of the pHi decrease by 81%. Nominal removal of basolateral HCO3- (replaced with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) inhibited the zero Na-induced depolarization by 64%, whereas nominal removal of Na+ inhibited the 2 mM HCO3-induced depolarization by 67%. Replacement of all basolateral Cl- with glucuronate did not inhibit the changes in Vbl induced by changing [HCO3-] or [Na+]. Observations similar to those described above have been made previously on Ambystoma proximal tubules, and attributed to an electrogenic Na/HCO3 cotransport mechanism that carries HCO3-, Na+, and net negative charge in the same direction. We conclude that Necturus proximal tubules possess a similar, if not identical, electrogenic Na/HCO3 cotransport mechanism.

Evidence for suppression of potassium conductance by noradrenaline in smooth muscle of guinea-pig vas deferens.

The ionic dependency was examined in the reversal potential of the NA-induced membrane depolarization of smooth muscle of the guinea-pig vas deferens, using the double sucrose-gap method. In the control (5.9 mM K) solution and solutions containing 20 and 60 mM K ions, replaced with equimolar amount of Na ions, the reversal potential was negative to the membrane potential at the steady state in each solution, by 19.5, 15.1 and 13.2 mV, respectively. Taking account that the higher external K concentration causes the larger membrane depolarization, these results indicate that the reversal potential shifted toward the positive direction as the external K concentration was increased. On the other hand, the calculated equilibrium potential of K ions in those solutions is -88, -52 and -24 mV, respectively. In those solutions, furthermore, the equilibrium potential of Na ions is 42, 38 and 29 mV, respectively. However, the equilibrium potentials of Ca and Cl ions should be unchanged. Therefore, it is suggested that the reversal potential of the NA-induced depolarization varied in the given different solutions compatibly only with the change in the K equilibrium potential. This provides evidence that in this tissue, NA induces a reduction in the K conductance of the cell membrane.

Noradrenaline mediates slow excitatory synaptic potentials in rat dorsal raphe neurons in vitro

Repetitive focal stimulation to the slice surface within the region of the dorsal raphe (DR) nucleus of rat brain elicited a slow excitatory synaptic potential (slow EPSP), which followed a slow inhibitory synaptic potential (slow IPSP) in a majority of the DR neurons. The slow EPSPs were associated with either an increase or a decrease in membrane resistance. Noradrenaline (NA) application caused a membrane depolarization in most of the DR neurons. The NA-induced depolarization was also accompanied by either an increase or a decrease in membrane resistance. Both the slow EPSP and NA-induced depolarization were inhibited by phentolamine and prazosin but not by yohimbine and propranolol. The result suggests that slow EPSPs in rat DR neurons are mediated by NA interacting with an α 1-adrenoceptor.

Possible mechanism of adrenergic and nonadrenergic inhibition in intestinal smooth muscle cells.

Nonadrenergic synaptic transmission in circular and longitudinal smooth muscles of caecum preexposed to K-free solution for 4-5 h has been studied by means of sucrose gap technique. In addition, the effects of noradrenaline (NA) and ATP on these muscles were investigated under these conditions. The action of the above substances was accompanied by depolarization and contraction. NA induced a decrease in the membrane resistance. Addition of 0.5 mM Ba2+ to K-free solution intensified the depolarization. 1 mM of Mn2+ blocked depolarization and contraction. Intramural stimulation produced noncholinergic e.j.p.s blocked by TTX. Addition of 0.5 mM Ba2+ increased their amplitude. A reversal potential of both NA-induced depolarization and e.j.p. was in the range of + 10 to + 20 mV. It is supposed that e.j.p.s and depolarization observed in response to ATP and NA action are due to an increase in calcium permeability of the membrane.

Decrease in membrane conductance induced by noradrenaline in the smooth muscle of guinea-pig vas deferens.

The electrical response of the smooth muscle of guinea-pig vas deferens to exogenously applied noradrenaline (NA) was examined using the double sucrose-gap method. NA evoked a depolarization of the smooth muscle membrane which was associated with an increase in the size of electrotonic potentials. A conditioning depolarization of the membrane induced by current application enhanced the size of NA-induced depolarization, whereas a conditioning hyperpolarization reduced it. When a conditioning hyperpolarization of 25 mV in magnitude was applied, the direction of potential change induced by NA was reversed. These results are discussed with respect to the ionic mechanism of the electrical event in response to NA in this tissue.

Effects of a new alpha-adrenoceptor blocking agent, ethyl-7-[4-(2-methoxyphenyl)-1-piperazinyl] heptanoate dihydrochloride (SGB-483), on smooth muscle and neuromuscular transmission in guinea-pig mesenteric artery.

The effects of ethyl-7-[4-(2-methoxyphenyl)-1-piperazinyl] heptanoate dihydrochloride (SGB-483) on the smooth muscle of the guinea-pig mesenteric artery were investigated using microelectrodes. The resting membrane potential was -70.3 +/- 2.1 mV.SGB-483 (10(-8)M - 10(-4)M) did not modify the membrane potential or membrane resistance, as estimated from measurement of current-voltage relationships. Noradrenaline (NA; above 10(-5)M) depolarized the membrane. After pretreatment with SBG-483 10(-5)M or prazosin 10(-6)M, the NA-induced depolarization of the membrane was inhibited; yohimbine (10(-5)M) was ineffective. Phenylephrine and NA (greater than 3 X 10(-7)M) but not clonidine (10(-6)M) contracted the artery. These contractions were inhibited by SGB-483. Following repetitive perivascular nerve stimulation, the amplitude of excitatory junction potentials (e.j.ps) increased to a certain steady state value (e.j.p.(s]. The amplitude of e.j.p.(s) was frequency-dependent. Application of SGB-483 (over 10(-8)M) enhanced the amplitude of e.j.p.(s), dose-dependently with no change in the amplitude of the first e.j.p. (e.j.p.(f] evoked by the first stimulus. After pretreatment with NA, the amplitudes of both e.j.p.(f) and e.j.p.(s) were inhibited, dose-dependently. Following pretreatment with SGB-483 (10(-6) - 10(-5)M), the NA-induced reduction in the amplitude of both e.j.p.(f) and e.j.p.(s) were reversed and the control values restored. Clonidine (10(-7)M) inhibited the amplitude of e.j.p.(f) and e.j.p.(s), and SGB-483 (10(-7)M) partially restored the amplitude of both. Yohimbine (10(-7)M) and phentolamine (10(-7)M) enlarged the amplitude of e.j.p.(s); the amplitude of e.j.p.(f) was inhibited by yohimbine and enlarged by phentolamine. Prazosin (10(-6)M) had no effect on the amplitude of either e.j.p.(f) or e.j.p.(s), at any given stimulus frequency. SBG-483 (10(-7)M) did not enhance the amplitudes of either e.j.p.(f) or e.j.p.(s) following pretreatment with phentolamine (10(-7)M) or yohimbine (10(-7)M) but did enhance the amplitude following pretreatment with prazosin (10(-7)M). SGB-483 possesses the property of an alpha 1- and alpha 2-adrenoceptor antagonist. The alpha-antagonistic action was apparent on post-junctional smooth muscle cells. The alpha 2-antagonistic action on neuromuscular transmission was mediated at pre-junctional nerve terminals to enhance the release of NA. The prejunctional actions of SGB-483 were more selective than those of yohimbine or phentolamine.

Effects of a new alpha-adrenoceptor blocking agent, ethyl-7-[4-(2-methoxyphenyl)-1-piperazinyl] heptanoate dihydrochloride (SGB-483), on smooth muscle cells and neuromuscular transmissions of the guinea-pig mesenteric artery.

Effects of SGB-483 on the smooth muscles of the guinea-pig mesenteriCgar-tery were investigated using the microelectrode method. SGB-483 (10−8-10−4M) did not modify either the membrane potential or resistance. The noradrenaline(NA)-induced(>10−5M) depolarization of the membrane was inhibited under pretreatment with SGB-483(10−5M) or prazosin(10−6 M), while yohimbine(10−5M) had no effect on the NA-induced depolarization. Phenylephrine and NA(>3×10−7M) produced contraction, which was inhibited by SGB-483, but Clonidine(10−6M) did not produce contraction. SGB-483(>10−8M) enhanced the amplitude of steady state e.j.p.(e.j.p.(s)), dose-dependently, with no change in the amplitude of the first e. j.p. (e. j.p. (f)). Pretreatment with SGB-483 restored the NA-induced reductions in the amplitudes of e.j.ps (f and s). Yohimbine(10−7M) and phentolamine(10−7M) enlarged the amplitude of e.j.p.(s), but the amplitude of e.j.p.(f) was inhibited by yohimbine and enlarged by phentolamine. Prazosin(10−6M) had no effect on the amplitudes of e.j.p.(f) and e.j.p.(s). Clonidine(10−7M) inhibited the amplitude of e.j.p.(f) and e.j.p.(s), and SGB-483(10−7M) partly restored the amplitudes of the e.j.ps evoked under both conditions. α1-Antagonistic actions were apparent in the case of postjunctional smooth muscle cells. (α2-Antagonistic action was apparent in the neuromuscular transmission process. SGB-483 acted on the prejunctional nerve terminals and enhanced the release of NA. Prejunctional actions of SGB-483 were more selective then those of yohimbine and phentolamine. SGB-483 seems to be a more selective α1 and α2-adrenoceptor antagonist than phentolamine.

Neuromuscular transmission and smooth muscle membrane properties in the guinea-pig ear artery.

Effects of noradrenaline and alpha-adrenoceptor blocking agents on neuromuscular transmission of the guinea-pig ear artery were assessed using the micro-electrode method.1. The mean membrane potential, and length and time constants of the longitudinally oriented muscle cells were -64.5 +/- 5 mV (n = 150), 1.03 +/- 0.16 mm (n = 15) and 410 +/- 40 msec (n = 7) respectively. From the current-voltage relationship, weak outward current pulses produced an anomalous rectification of the membrane while stronger intensities produced a normal rectification of the membrane with a depolarization over 10-15 mV.2. Brief stimulation (0.1-0.5 msec) of the tissue produced an excitatory junction potential (e.j.p.). Facilitation produced by repetitive stimulation was evident only on very rare occasions. Higher stimulus intensities caused a stepwise increase of the amplitude of e.j.p.s.3. Spontaneously generated miniature excitatory junction potentials (m.e.j.p.s) were recorded from the muscle membrane. In many cells, the interval and amplitude histograms of m.e.j.p.s showed skew curves. On rare occasions, a bell-shaped amplitude distribution (quantal release of packeted noradrenaline (NA)) was observed.4. NA (> 3 x 10(-7)m) depolarized the membrane and increased the membrane resistance, as measured from the amplitude of the electrotonic potential. Phentolamine suppressed the NA-induced depolarization. However, high concentrations of phentolamine (> 10(-5)m) depolarized the membrane and increased the membrane resistance.5. NA (10(-8)m) caused no change in membrane potential though it suppressed the amplitude of an e.j.p. produced by a single stimulus, but did not suppress the amplitude of the subsequent e.j.p.s evoked by repetitive stimulation (0.2-2.0 Hz). A higher concentration of NA (3 x 10(-7)m) depolarized the membrane and markedly suppressed the amplitude of e.j.p.s. On the other hand, NA (10(-8) or 2 x 10(-8)m) generated burst discharges of m.e.j.p.s between silent periods or random generation.6. Phentolamine (10(-6)m) markedly enhanced the amplitude of e.j.p.s and caused a smooth facilitation in response to a train of stimuli with no effect on the membrane potential. A stepwise change in the amplitude of e.j.p.s was no longer observed at any given stimulus frequency and intensity.7. Phenoxybenzamine (10(-7)m) suppressed the amplitude of e.j.p.s with no change in the membrane potential.8. The results led to the conclusion that, at a concentration which has no effect on the post-junctional muscle membrane, NA and phentolamine seemed to be more effective on prejunctional adrenoceptors, while phenoxybenzamine seemed to have a greater effect on post-junctional adrenoceptors. NA depresses adrenergic transmission by negative feed-back, while the enhancing action of phentolamine can be explained partly by blocking of prejunctional adrenoceptors and, in addition, by an increase of NA release.

Effects of vasopressin on smooth muscle cells of guinea-pig mesenteric vessels.

1 The effects of vasopressin on the membrane and contractile properties of smooth muscle cells of guinea-pig mesenteric arteries, and mesenteric and portal veins were investigated in various ionic environments by means of a micro-electrode technique and an isometric tension recording method. The results were compared with those obtained with oxytocin and noradrenaline (NA).2 In the mesenteric jejunal artery, the mean membrane potential was -56.6 +/- 2.3 mV, s.d, and the membrane was electrically quiescent. Application of outward current pulses generated small graded responses, and the current voltage relationship was linear with application of an inward current pulse.3 Vasopressin and NA depolarized the membrane and increased the membrane resistance. Vasopressin was a 1000 times more potent than oxytocin in depolarizing the membrane. In high concentrations, vasopressin (1 x 10(-3) or 1 x 10(-2) iu/ml) or NA (5.9 x 10(-5) M) generated slow oscillatory membrane potential changes (slow waves) and spikes during the depolarization. The excitatory actions of vasopressin and NA were not suppressed by tetrodotoxin (3.1 x 10(-7) M) or ouabain (1.3 x 10(-6) M) and the actions of vasopressin were not suppressed by adrenoceptor blocking agents (3.9 x 10(-7) M phentolamine or 3.6 x 10(-7) M propranolol).4 The depolarization induced by vasopressin or NA is mainly due to a decrease in the K-permeability of the membrane. However, the contribution of other ionic species to the depolarization induced by vasopressin or NA differed, e.g. in low concentrations of [Na](o), the NA-induced depolarization was suppressed to a greater extent than that due to vasopressin. In low concentrations of [Ca](o), the vasopressin-induced depolarization was suppressed to a greater extent than with NA.5 In low concentrations of [Ca](o) and in the presence of vasopressin or NA, spike generation was inhibited but slow waves were not. In low concentrations of [Na](o), the vasopressin-induced slow waves and spikes were for the great part preserved, but with a high concentration of [Ca](o), vasopressing-induced slow waves were suppressed.6 Both vasopressin and NA produced contractions in the jejunal mesenteric artery. However, the maximum contraction in response to vasopressin was larger than that to NA, although both induced similar membrane depolarization. In a low concentration of [Na](o), vasopressin but not NA produced a contraction.7 In the cranial mesenteric artery, NA (5.9 x 10(-5) M) depolarized the membrane and produced a contraction, while vasopressin (1 x 10(-1) iu/ml) and oxytocin (1 x 10(-1) iu/ml) neither depolarized the member nor produced a contraction. In the mesenteric vein, NA (5.9 x 10(-5) M) slightly depolarized the membrane and produced a small contraction. On the other hand, in the portal vein, NA (5.9 x 10(-7) M) produced a marked depolarization and a contraction. Vasopressin (1 x 10(-1) iu/ml) and oxytocin (1 x 10(-1) iu/ml) produced neither excitatory nor inhibitory actions in these veins.8 It is concluded that vasopressin acts on only small muscular arteries, while NA acts on all mesenteric vessels, particularly the portal vein. Therefore, the hepatic portal vascular resistance may be increased by NA and reduced by vasopressin.