Neuropeptide Y and sympathetic control of heart contractility and coronary vascular tone

The effects of neuropeptide Y (NPY) on contractility of the spontaneously beating guinea-pig atrium and transmural nerve stimulation (TNS)-induced efflux of tritium-noradrenaline (3H-NA) were studied in vitro. NPY induced a moderate positive chronotropic and inotropic atrial response, which was resistant to metoprolol. TNS at 2 Hz for 2 s caused an increase in rate and contractile force. These effects were significantly reduced by NPY. NPY also reduced the TNS induced (2 Hz for 20 s), fractional [3H]NA release by 40% without affecting the contractile response. The contractile effects of exogenous NA on the guinea-pig atrium were not affected by NPY. NPY caused a long-lasting increase in coronary perfusion pressure, and also, in high doses, an inhibition of ventricular contractility in the isolated, perfused guinea-pig heart. The perfusion pressure increase to NPY, which most likely reflects coronary vasoconstriction, was resistant to alpha- and beta-adrenoceptor blockade but sensitive to the calcium antagonist nifedipine. A 50% reduction of the vascular NPY response occurred at 10(-9) M nifedipine, which did not influence cardiac contractility per se or the contractile effects of NA. NPY did not modify the increase in ventricular contractility induced by NA. Noradrenaline did not influence coronary perfusion pressure after beta-blockade. Since NPY is present together with NA in cardiac nerves, it may be suggested that NPY is involved in the regulation of NA release as well as the sympathetic control of atrial contractility and coronary blood flow.     

Effects of neuropeptide Y (NPY) on mechanical activity and neurotransmission in the heart, vas deferens and urinary bladder of the guinea-pig

The effects of preincubation for 10 min with synthetic porcine neuropeptide Y (NPY) on muscle tone and autonomic transmission in the guinea-pig right atrium, vas deferens, urinary bladder, portal vein and trachea were analysed in vitro. NPY induced a metoprolol-resistant, long-lasting, positive inotropic and chronotropic effect per se in the spontaneously beating right atrium. Furthermore, NPY caused a reversible inhibition of both the metoprolol and atropine-sensitive auricle responses to field stimulation (2 Hz or 4 Hz for 2 s) without affecting the response to exogenous noradrenaline (NA) or acetylcholine (ACh). NPY did not induce any contraction of the vas deferens, but inhibited both the rapid twitch response and the sustained tonic contraction induced by field stimulation. The NPY-induced inhibition of the tonic contraction was more long-lasting than that of the twitch response. The tonic contraction was blocked by phentolamine and the twitch response by alpha-, beta-methylene ATP tachyphylaxis. NPY did not inhibit the contractile effects of NA, ATP or alpha-, beta-methylene ATP. NPY also induced a reversible reduction of the non-cholinergic, non-adrenergic contractile response to field stimulation of the urinary bladder. In the portal vein, NPY (up to 5 X 10(-7) M) did not inhibit the spontaneous motility or the phentolamine-sensitive contractile responses to field stimulation and NA. The atropine-sensitive contraction of the trachea or the non-adrenergic, non-cholinergic relaxation induced by field stimulation were not significantly influenced by NPY in doses up to 5 X 10(-7) M.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of extracellular calcium and nifedipine on alpha 1- and alpha 2-adrenoceptor-mediated contractile responses in isolated rat and cat cerebral and mesenteric arteries

The influence of extracellular Ca2+ and nifedipine on contractile responses to 10 microM noradrenaline (NA) was investigated in isolated rat and cat middle cerebral (RCA, CCA) and mesenteric (RMA, CMA) arteries. In the CCA (containing predominantly alpha 2-adrenoceptors), the NA-induced contractions developed considerably more slowly than in the RCA, RMA (containing mainly alpha 1-adrenoceptors) and CMA (sensitive to both alpha 1- and alpha 2-adrenoceptor selective antagonists). The tonic component of the NA-induced contraction in the four types of artery was substantially suppressed after only short periods in Ca2+-free solution. In each type of artery, excluding the CCA, the contractile response to 124 mM K+ was more sensitive to Ca2+ deprivation than that to NA. This suggests that NA, besides mobilizing extracellular Ca2+, can also release Ca2+ from an intracellular pool in the RCA, RMA and CMA, but not in the CCA. Thus, alpha 1-adrenoceptor-mediated contractions in the RCA and RMA seem to depend on both Ca2+ influx and intracellular Ca2+ release, whereas alpha 2-adrenoceptor-mediated contractile responses in the CCA appear to rely almost entirely on Ca2+ influx. Both the maximum response and the tonic component of the NA-induced contraction were significantly more sensitive to nifedipine in the CCA than in the RCA. In comparison with the NA-induced contractions in these arteries, those in the RMA and CMA were relatively resistant to nifedipine. In the CCA exposed to NA in Ca2+-free medium, nifedipine almost abolished the contraction induced by re-addition of Ca2+, whereas in the other types of artery, Ca2+ re-application evoked a significant contraction also in the presence of the drug. The differential effects of nifedipine presumably reflect differences between the arteries, not only in the relative contribution of Ca2+ influx and intracellular Ca2+ release to the contractile activation, but also in the nifedipine sensitivity of the Ca2+ entry pathways utilized by NA. It is concluded that the mechanisms through which NA induces contraction seem to be related both to the subtype of alpha-adrenoceptor stimulated by NA and to the type of vessel studied.     

Characterization of the contractile effect of neuropeptide Y in feline cerebral arteries

The action of neuropeptide Y (NPY), which coexists with noradrenaline (NA) in perivascular sympathetic nerves, has been examined on feline cerebrovascular smooth muscle using a sensitive in vitro system. The direct cerebrovascular responses of peptides with structural similarities with NPY, peptide YY (PYY), avian (APP), and bovine (BPP) and human (HPP) pancreatic polypeptides, have been compared with that of NPY on isolated feline cerebral arteries. The relative potency for contractions induced by the peptides is: NPY, PYY greater than APP greater than BPP, HPP. The alpha-adrenoceptor antagonist rauwolscine, which blocked the response to noradrenaline (NA), had no effect on NPY-induced contractions. Neuropeptide Y significantly potentiated contractions induced by 10(-6) M NA, but not by 10(-5) M. Withdrawal of Ca2+ from the extracellular medium for 30 min reduced the contractile response to NPY in cerebral vessels by about 80%. Subsequent readdition of Ca2+ caused reproducible contractions which were inhibited by the calcium entry blocker nimodipine. Nimodipine also relaxed isolated middle cerebral artery segments contracted by NPY and NA in a concentration-dependent manner. The data suggest that NPY mediates contraction of cerebrovascular smooth muscle via a mechanism that is dependent on the concentration of extracellular calcium.     

Effects of sodium depletion on contractions evoked in intact and skinned muscles of the guinea-pig mesenteric artery

In the guinea-pig mesenteric artery, reduction in [Na]o by 30 mM (substituted by choline or sucrose; 137 mM [Na]o in Krebs solution) generated contraction with no change in membrane potential. In NaCl-free solution (15 mM [Na]o), the amplitude of phasic contraction reached 0.8 times the contraction evoked by 118 mM [K]o with only a slight depolarization. In NaCl-free solution, the amplitude of phasic contraction evoked by noradrenaline (NA) 5 X 10(-5) M or caffeine 5 mM increased to roughly twice the amplitude of the contraction evoked in the control solution. In Ca-free solution, the K-, NaCl-free- or Na-free-induced contractions rapidly ceased, but NA-induced contraction ceased within 5 min and the caffeine-induced contraction persisted for more than 15 min. In a skinned fiber, increase of [Na]o from 10 to 60 mM suppressed the pCa-tension relationship in the ranges of 10(-7) and 10(-5) M free Ca but not with a dose of 30 mM [Na]o. NA (10(-5) M) had no effect on skinned fibers. Increase in Na concentration (60 mM) had no effect on Ca accumulation in the store site or on Ca release by caffeine. Possible Na-related mechanisms on the development of mechanical response are discussed in relation to Ca on the surface and in the internal membrane structure. The NaCl-free-induced contraction in smooth muscles of the guinea-pig mesenteric artery is postulated to be due to influx of Ca through the Na channel, rather than the Ca channel.     

Contractile effects of various vasoactive agents in small rat portal veins and hepatic arteries and the influence of sympathetic denervation on the noradrenaline response

Contractile responses were studied in isolated tubal segments of branches of the rat portal vein (luminal diameter approximately 300 microns) and hepatic artery (luminal diameter approximately 200 microns). Portal veins were approximately three times more sensitive to noradrenaline (NA) than hepatic arteries. 5-hydroxytryptamine contracted hepatic arteries concentration-dependently, whereas it produced only weak and inconsistent contractions in portal veins. Vasopressin effectively contracted hepatic arteries, whereas it had no effect on portal veins. Both vessel types responded to prostaglandin F2 alpha with contractions, although the drug potency was relatively low (EC50 greater than 10(-5) mol l-1). Histamine and carbachol failed to induce (hepatic arteries) or caused only weak (portal veins) contractions. Microsurgical hepatic hilar denervation reduced the catecholamine content of the parenchyma to less than or equal to 25% of controls. In both portal veins and hepatic arteries, the denervation procedure increased the NA sensitivity by factors of 3.1 and 2.0, respectively. In non-denervated livers, cocaine produced a similar increase of the NA sensitivity, whereas the drug had no significant effect in vessels from denervated animals. Thus, there was a marked difference between rat portal veins and hepatic arteries in their responsiveness to several contractile agents. Furthermore, the results of the present study indicate that the adrenergic nerves in both vessel types can be adequately removed by the microsurgical denervation procedure used.     

Longitudinal Propagation of Myogenic Activity in Rabbit Arteries and in the Rat Portal Vein

Longitudinal spread of induced activity was analysed in the rat portal vein and rabbit aorta and compared to propagation in the brachial, radial, ear, mesenteric, femoral and posterior tibial arteries of the rabbit. Isometric force in spiral strips or intact preparations was measured during superfusion with Krebs' solution. The lower 20 per cent of the preparation could be selectively exposed to exogenous noradrenaline (NA) or to transmural field stimulation. Propagation was inferred to occur when the amplitude of the local response, relative to that when the entire preparation was stimulated, exceeded the relative length of the locally stimulated tissue. No propagation was found in the rabbit aortic strip. Propagation was less in proximal than in distal muscular arteries. The calculated distance of propagation was greatest in the rat portal vein. The intact limb vessel preparations reponded to NA with phasic contractions. In the ear artery, here was propagation only of the first phase of this biphasic response. These results show that different sections of the rabbit vascular tree display individuality in their ability to support propagation. In general, propagation in the arterial tree appears to be greatest in the smaller vessels.     

Regulatory mechanisms for the spontaneous contractile force and frequency of the rat portal vein]

By the extracellular recording technique, the action potentials and spontaneous contractions of the isolated rat longitudinal portal vein strips were simultaneously recorded in the presence of varying concentrations of electrolytes, various vasoactive agents, and hormones, and the mechanisms regulating the force and frequency of spontaneous contraction of the vascular smooth muscle were investigated. A longitudinal stretch (-200% of the initial length), a higher [K+]0 (-30 mM), a lower [Na+]0, epinephrine, acetylcholine or ouabain increased both force and frequency of the phasic contractions. A lower [Na+]0 or ouabain raised basal tone of the muscle in addition to the above effects. A higher [Ca++]0 increased the contractile force, while it decreased the frequency. A lower [Ca++]0, calcium channel blocker or VIP reduced the contractile force but increased the contractile frequency. A bigger force and a higher frequency of the phasic contractions were exhibited in the portal vein strips isolated from rats with CCl4-induced experimental portal vein hypertension. They were similar to responses of the strips from the intact rats to stretch, ouabain, or higher [Ca++]0 in the presence of lower [Na+]0. These results suggest that an initiation and force of the phasic and tonic contractions depend on extracellular Ca++ concentration and influx of Ca++, and frequency of the phasic contractions, mainly on membrane potential rather than on extracellular Ca++ concentration. In the portal hypertension, permeability of the cell membrane to Ca++ is possibly increased.     

The effect of length on the sensitivity to phenylephrine and calcium in intact and skinned vascular smooth muscle

The length dependency of the sensitivity to activators of the smooth muscle of different blood vessels is not yet fully understood. Muscle preparations of the aorta, the femoral artery and the portal vein of the rabbit were investigated for the length dependency of the sensitivity to phenylephrine and calcium in both intact and triton X- 100 skinned preparations. For intact smooth muscles we found that at increased preparation length, the sensitivity of contraction was increased. The femoral artery showed the largest effect and the portal vein the smallest. In the skinned preparations of the three preparations the calcium sensitivity was not dependent on the preparation length. We conclude that the changes of the sensitivity in intact preparations are not caused by changes of the calcium sensitivity of the contractile proteins.     

Effects of prostanoids on isolated feline cerebral arteries. II. Roles of extra- and intracellular calcium for the prostaglandin F2 alpha-induced contraction

The roles of extra- and intracellular calcium for the contractile effects of PGF2 alpha in the feline basilar artery (BA) were investigated. Comparisons were made with contractions induced by K+ and noradrenaline (NA). Addition of nifedipine to PGF2 alpha- or K+ (124 mM)-contracted arteries resulted in an incomplete relaxation, whereas NA-contracted vessels were completely relaxed. Incubation of the preparations in a calcium-free medium containing 10(-5) M EGTA for 5-10 min almost abolished contractions induced by K+ and NA. In contrast, 63% of the response to PGF2 alpha remained after pretreatment of the arteries in a calcium-free solution for 40 min; PGF2 alpha produced a biphasic contraction in 17 out of 20 preparations consisting of a rapidly developing initial phase followed by a second increase in tension after 1-6 min. The second phase was absent if the EGTA-concentration was increased to 10(-4) M, or if the arteries were pre-treated with nifedipine. After incubation of the arteries in a calcium-free medium for 40-120 min and K+-depolarization, re-addition of calcium elicited contractions at lower concentrations in the presence of PGF2 alpha than in controls. The results suggest that PGF2 alpha-induced contractions in the feline BA are considerably less dependent on extracellular calcium than contractions evoked by K+ or NA. PGF2 alpha appears to be able to release calcium from two cellular stores, and may also promote calcium influx through the cell membrane.     

Clonidine induced endothelium-dependent tonic contraction in circular muscle of the rat hepatic portal vein.

Clonidine, an alpha2-agonist, has been shown to be useful in the treatment of hepatic portal hypertension in cirrhosis. The mechanism has been attributed to a clonidine-induced decrease in sympathetic activity. While clonidine has been shown to stimulate the alpha2-adrenoceptors of blood vessels, there is limited knowledge of the effects of clonidine on the circular muscle of the hepatic portal vein which regulates its blood flow. To investigate clonidine-induced contraction of the circular muscle of the hepatic portal vein and to clarify the possible role of the endothelium in the contraction, we examined the effects of clonidine on the isometric contraction of endothelium-intact and -removed ring preparations of the rat hepatic portal vein. In endothelium-intact preparations, clonidine caused a concentration-dependent increase in the amplitude of contractions. Inhibition of NO synthesis with Nomega-nitro-L-arginine (L-NNA) elevated the resting tone, and increased the amplitude of the clonidine-induced contractions. Inhibition of cyclooxygenase by diclofenac did not change the amplitude of the clonidine-induced contractions observed both in the presence and absence of L-NNA. Application of a single concentration of clonidine induced a clear increase in amplitude of both twitch and tonic contractions. Twitch and tonic contractions induced by clonidine were inhibited by yohimbine. When the endothelium was damaged by sodium deoxycholate, tonic contractions induced by clonidine were completely suppressed, whereas the increase in twitch contractions was not influenced by chemical damage of the endothelium. Neither SKF-96365, a nonselective cation channel blocker, nor superoxide dismutase, a free radical scavenger, in the presence of catalase, changed the tonic contraction induced by clonidine. These results indicate that stimulation of alpha2-adrenoceptors enhanced twitch contractions and induced tonic contractions in the circular muscle of the rat hepatic portal vein, especially in the absence of NO. The latter, but not the former, occurs through an endothelium-dependent pathway.     

Analysis of the effects of graded levels of hypoxia on noradrenaline-evoked contraction in the rat iliac artery in vitro

In rings of rat iliac artery, contractions were evoked by noradrenaline (NA), the selective alpha(1) adrenoceptor agonist phenylephrine (PE), and K(+), which causes depolarisation-induced contraction. There was no evidence of alpha(2) adrenoceptor-evoked contraction. Hypoxia, induced by reducing P(O(2)) in the bath from 100 mmHg to 70, 55 or 40 mmHg, had similar effects on rings with (E+) and without (E-) endothelium. In E- rings, the NA concentration-response curve was biphasic, whereas that for PE was monophasic. Hypoxia reduced maximum contractions in response to NA and PE (NA(max) and PE(max), respectively) without affecting the concentrations that evoked 50 % of maximum contraction (EC(50)). At P(O(2)) of 70 mmHg, NA(max) of the high affinity alpha(1) receptor for NA (NA(maxh)) and PE(max) were reduced by approximately 15 %, but at P(O(2)) of 55 and 40 mmHg, NA(maxh) was severely attenuated while PE(max) fell by 45 and 75 %, respectively. Similarly, the Ca(2+) channel blocker nicardipine depressed NA(maxh) and PE(max), but P(O(2)) of 55 mmHg further reduced NA(max) and PE(max). Hypoxia also reduced contractions evoked by NA, PE or K(+) at the concentrations required to produce 80 % of the maximum contraction (EC(80)), receptor-mediated contractions being more affected. Ca(2+)-free conditions reduced the contractions evoked by NA and PE, at the EC(80), to approximately 10 % of control. The K(+) channel inhibitors glibenclamide and tetraethylammonium did not prevent hypoxia-induced depression of PE-evoked contraction. Thus, contractions evoked in iliac artery by the high affinity subtype of alpha(1) adrenoceptor for NA, which may respond to circulating levels of NA, and by the single alpha(1) adrenoceptor subtype for PE, are especially vulnerable to P(O(2)) levels less-than-or-equal 55 mmHg. We propose that this reflects hypoxia-induced inhibition of Ca(2+) influx through L-type and receptor-operated Ca(2+) channels; K(+) channel opening makes little contribution.     

Influence of extracellular calcium and nifedipine on α1-and α2-adrenoceptor-mediated contractile responses in isolated rat and cat cerebral and mesenteric arteries

The influence of extracellular Ca²⁺ and nifedipine on contractile responses to 10 μM noradrenaline (NA) was investigated in isolated rat and cat middle cerebral (RCA, CCA) and mesenteric (RMA, CMA) arteries. In the CCA (containing predominantly α₂-adrenoceptors), the NA-induced contractions developed considerably more slowly than in the RCA, RMA (containing mainly α₁-adrenoceptors) and CMA (sensitive to both at,- and α₂-adrenoceptor selective antagonists). The tonic component of the NA-induced contraction in the four types of artery was substantially suppressed after only short periods in Ca²⁺-free solution. In each type of artery, excluding the CCA, the contractile response to 124 mM K⁺ was more sensitive to Ca²⁺ deprivation than that to NA. This suggests that NA, besides mobilizing extracellular Ca²⁺, can also release Ca²⁺ from an intracellular pool in the RCA, RMA and CMA, but not in the CCA. Thus, α₁-adrenoceptor-mediated contractions in the RCA and RMA seem to depend on both Ca²⁺ influx and intracellular Ca²⁺ release, whereas α₂-adrenoceptor-mediated contractile responses in the CCA appear to rely almost entirely on Ca²⁺ influx. Both the maximum response and the tonic component of the NA-induced contraction were significantly more sensitive to nifedipine in the CCA than in the RCA. In comparison with the NA-induced contractions in these arteries, those in the RMA and CMA were relatively resistant to nifedipine. In the CCA exposed to NA in Ca²⁺-free medium, nifedipine almost abolished the contraction induced by re-addition of Ca²⁺, whereas in the other types of artery, Ca²⁺ re-application evoked a significant contraction also in the presence of the drug. The differential effects of nifedipine presumably reflect differences between the arteries, not only in the relative contribution of Ca²⁺ influx and intracellular Ca²⁺ release to the contractile activation, but also in the nifedipine sensitivity of the Ca²⁺ entry pathways utilized by NA. It is concluded that the mechanisms through which NA induces contraction seem to be related both to the subtype of α-adrenoceptor stimulated by NA and to the type of vessel studied.     

Different effects of neuropeptide Y on electrically induced contractions in the longitudinal and circular smooth muscle layers of the female rabbit urethra

The effects of neuropeptide Y (NPY) on preparations of isolated longitudinal and circular smooth muscle from rabbit urethra were studied. In both types of muscle, electrically induced contractions and relaxations could be abolished by tetrodotoxin, (TTX). In the longitudinal muscle preparations the contraction was slightly reduced by prazosin, but markedly reduced by scopolamine and NPY. The NPY effect was not influenced by pretreatment with rauwolscine. Pretreatment with NPY had no effect on contractions induced by noradrenaline (NA) or carbachol and the peptide did not relax preparations contracted by these agents. In circular muscle an initial, fast response, not sensitive to prazosin or scopolamine was occasionally observed following electrical stimulation. A slow contraction component was regularly seen; this response was abolished by prazosin. Neuropeptide Y did not influence any of these responses. The preparations were concentration-dependently contracted by NA, whereas carbachol had no effect. Pretreatment with NPY did not affect contractions induced by NA, nor did the peptide relax NA-contracted preparations. In neither longitudinal nor circular muscle strips did NPY affect the electrically induced TTX sensitive relaxation of NA-contracted preparations. The results suggest that in the rabbit urethra NPY reduces contractions in the longitudinal muscle layer by selectively inhibiting the release of acetylcholine from cholinergic nerves. Neuropeptide Y did not appear to have any significant postjunctional effects nor to interfere with the release, or effects of NA or other transmitter agents. The physiological importance of the urethral effects of NPY remains to be established.     

Responses to potential vasoactive substances of isolated mammary blood vessels from lactating sows

The purpose of the investigation was to examine the response of the milk vein and the mammary artery to potential vasoactive substances in lactating sows. The response on artery and vein segments from the same sow was measured for the following substances: noradrenaline (NA), serotonin (5-HT), prostaglandin F2alpha (PGF2alpha), prostacyclin (PGI2), histamine (Hi) and potassium (K+). Interestingly, the contractile force in the mammary vein segments expressed per weight unit (mN/mg) was 1.5-2.5 fold larger than in the artery segments when NA, 5-HT and PGF2alpha were used, but similar for K+, Hi and PGI2. In vein segments, the order of sensitivity to the substances expressed by their pD2 values was 5-HT > NA = PGF2alpha > Hi > K+. The present findings suggest that NA, 5-HT, PGF2alpha, PGI2, and Hi are involved in mammary blood flow regulation in the sow, and the mammary venous system may be as important as the mammary arterial system in this regulation.     

Diverse properties of store-operated TRPC channels activated by protein kinase C in vascular myocytes

In vascular smooth muscle, store-operated channels (SOCs) contribute to many physiological functions including vasoconstriction and cell growth and proliferation. In the present work we compared the properties of SOCs in freshly dispersed myocytes from rabbit coronary and mesenteric arteries and portal vein. Cyclopiazonic acid (CPA)-induced whole-cell SOC currents were sixfold greater at negative membrane potentials and displayed markedly different rectification properties and reversal potentials in coronary compared to mesenteric artery myocytes. Single channel studies showed that endothelin-1, CPA and the cell-permeant Ca(2+) chelator BAPTA-AM activated the same 2.6 pS SOC in coronary artery. In 1.5 mM [Ca(2+)](o) the unitary conductance of SOCs was significantly greater in coronary than in mesenteric artery. Moreover in 0 mM [Ca(2+)](o) the conductance of SOCs in coronary artery was unaltered whereas the conductance of SOCs in mesenteric artery was increased fourfold. In coronary artery SOCs were inhibited by the protein kinase C (PKC) inhibitor chelerythrine and activated by the phorbol ester phorbol 12,13-dibutyrate (PDBu), the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) and a catalytic subunit of PKC. These data infer an important role for PKC in activation of SOCs in coronary artery similar to mesenteric artery and portal vein. Anti-TRPC1 and -TRPC5 antibodies inhibited SOCs in coronary and mesenteric arteries and portal vein but anti-TRPC6 blocked SOCs only in coronary artery and anti-TRPC7 blocked SOCs only in portal vein. Immunoprecipitation showed associations between TRPC1 and TRPC5 in all preparations but between TRPC5 and TRPC6 only in coronary artery and between TRPC5 and TRPC7 only in portal vein. Finally, flufenamic acid increased SOC activity in coronary artery but inhibited SOCs in mesenteric artery and portal vein myocytes. These data provide strong evidence that vascular myocytes express diverse SOC isoforms, which are likely to be composed of different TRPC proteins and have different physiological functions.     

Adrenoceptors mediating contraction in the human uterine artery

Pharmacological characterization of adrenoceptors mediating smooth muscle contraction was performed in isolated preparations from the human uterine artery. The mixed alpha 1- and alpha 2-adrenergic agonist, noradrenaline (NA) and the selective alpha 1-agonists, phenylephrine and methoxamine, all contracted the smooth muscle preparations in a concentration-dependent manner. The responses were antagonized competitively by the selective alpha 1-antagonist, prazosin, yielding pA2 values for the three agonists (8.33-9.08) typical for an interaction with alpha 1-receptors. The alpha 2-selective receptor agonists, clonidine and BHT 920, did not exert any contractile effects in the isolated uterine arteries, and the alpha 2-adrenergic antagonist, yohimbine, counteracted the contractile effect of NA only at high concentrations. The concentration-response curve for NA was unaffected by the alpha 2-selective antagonists, rauwolscine and idazoxan. The results suggest that the postjunctional contractile receptors in the human uterine artery primarily are of the alpha 1 type, and give no evidence for any substantial involvement of alpha 2-receptors in this important tributary vessel of the human female reproductive tract.     

Catecholamine fluorescent, acetylcholinesterase positive and peptide immunoreactive nerve fibers in the rat hepatic portal system

Innervation of rat hepatic portal system consisting of stem (portal vein) and peripheral portions (superior mesenteric vein, inferior mesenteric vein, splenogastric vein) was investigated by catecholamine fluorescence, acetylcholinesterase and immunohistochemical methods. Catecholamine fluorescent and Neuropeptide Y (NPY) immunoreactive (ir) nerve fibers were distributed throughout the hepatic portal system. Greater density was demonstrated in the peripheral portions. Catecholamine fluorescent and NPY ir nerve fibers formed ground plexus around the hepatic portal system. Acetylcholinesterase positive and vasoactive intestinal polypeptide-ir nerve fibers were sparsely distributed and no significant difference in density was noticed in the stem and the peripheral portions. Density of substance P ir, neurokinin A ir and calcitonin gene-related peptide ir nerve fibers was greater in the peripheral than the stem portion. All these fibers reticular showed pattern.     

Comparative effects of some calcium-channel blockers on human peripheral arteries and veins

We investigated the effects of five different calcium-channel blockers (CCBs), verapamil, nifedipine, diltiazem, flunarizine and lidoflazine, on contractions evoked in vitro by noradrenaline (NA) in small human arteries and veins from the epigastric region. Vessels were obtained from patients without obvious vascular diseases undergoing surgery because of inguinal hernias. The human superficial epigastric artery has previously been shown to contain mainly alpha 1-adrenoceptors, whereas in the vein alpha 2-adrenoceptors predominate. In experiments where NA (10(-5) M) was added non-cumulatively, it was found that nifedipine was the most potent relaxant agent in both arteries and veins, but that this drug showed no preference for any type of vessel. In contrast verapamil (10(-6) M) and (10(-5) M) diltiazem, flunarizine and lidoflazine inhibited the NA-induced contractions to a significantly greater extent in the arteries than in the veins. Comparison between diltiazem and nifedipine on contractions induced by cumulative addition to NA showed that both drugs had significantly more depressive effects on arteries than on veins if the vessels were contracted by relatively high concentrations of NA (10(-6) and 10(-5) M). The results thus confirm the clinical finding that CCBs have more pronounced effects on the arterial than on the venous side of the circulation. They do not support the view that CCBs are more effective inhibitors of alpha 2- than alpha 1-adrenoceptor mediated contraction in isolated human blood vessels.     

Distribution of cGMP-dependent and cGMP-independent Ca2+-activated Cl− conductances in smooth muscle cells from different vascular beds and colon

In the present patch-clamp study we have, for the first time, shown the tissue distribution of a recently characterized cGMP-dependent Ca²⁺-activated Cl^– conductance [18] in smooth muscle cells freshly isolated from different regions: aorta, pulmonary artery, tail artery, femoral artery, femoral vein, middle cerebral artery, renal artery, portal vein, superior mesenteric artery, mesenteric small artery and colon. The cGMP-dependent Cl^– conductance has properties distinct from those of the classical Ca²⁺-activated Cl^– conductances; their different sensitivities to niflumic acid and zinc were here utilized to distinguish them. They were found to be co-expressed in different patterns in smooth muscle cells of different origins. The cGMP-dependent conductance was greater in myocytes from cerebral artery and femoral vein and was greater in the renal artery, aorta, mesenteric small artery, femoral artery and the superior mesenteric artery. The presence of the cGMP-dependent Ca²⁺-activated Cl^– current in smooth muscle cells isolated from the colon demonstrates that this conductance is not limited to the vasculature. The classical Ca²⁺-activated Cl^– conductance was strongly expressed in smooth muscle cells from the portal vein and the tail artery, and noticeably higher in the pulmonary artery.