Biomedical subjects

L M Ren

Publications and source records attributed to L M Ren.

At least 19 recordsLinked to original sources

PubMed2001

Uridine triphosphate prolongs action potential duration of guinea pig papillary muscles via P2Y2 purinoceptors.

AIM: To study the electrophysiologic effects of uridine triphosphate (UTP) on the guinea pig papillary muscles in vitro and purinoceptors related with the action of UTP. METHODS: Intracellular microelectrode method was used to record action potentials (AP) in guinea pig papillary muscles. RESULTS: UTP, adenosine triphosphate (ATP), and adenosine diphosphate (ADP) prolonged the action potential duration (APD) concentration dependently in guinea pig papillary muscles. The potency order was UTP=ATP > ADP. There was cross desensitization between the response to ATP and that to UTP, and neither Ado nor alpha, beta-MeATP caused great change in AP of the papillary muscles. The prolongation of APD by UTP was not affected by sustained perfusion with aminophylline. As an osmotic pressure control equivalent to UTP 3 mmol/L, ceftriaxonum 3 mmol/L or NaCl 9 mmol/L induced a marked but slight prolongation of APD. CONCLUSION: UTP produced APD prolongation through specific and nonspecific actions, and the specific response to UTP was mediated by P2Y2 purinoceptors.

Action Potentials↗

PubMed2001

Sympathetic cotransmission in rabbit saphenous artery in vitro: effect of electric stimulation and potentiation by alpha,beta-methylene ATP.

AIM: To analyze the cotransmission characteristics of contractile responses to electric field stimulation with submaximal voltage and short train in the rabbit saphenous artery. METHODS: Isometric vasoconstriction of the rabbit saphenous arterial rings was recorded, and the sympathetic nerves of the arterial rings were activated with electric field stimulation. RESULTS: Electric stimulation produced contractile responses in a frequency-dependent manner in the rabbit saphenous artery. Selective alpha1-adrenoceptor antagonist, prazosin (1 micromol/L) did not affect the vasoconstriction induced by electric stimulation at 2 Hz significantly, but inhibited 39.9 % - 53.8 % of the vasoconstriction at 8 - 16 Hz. On the other hand, desensitization of the P2X1 receptor with alpha,beta-methylene ATP (3 micromol/L) abolished all the vascular responses induced by stimulation at 2 Hz, and obviously potentiated those induced by stimulation at 16 Hz, but it did not affect the concentration-dependent response curves for exogenous norepinephrine. The vasoconstriction responses induced by electric stimulation were all abolished by the treatment of a combination of prazosin (1 micromol/L) and alpha,beta-methylene ATP (3 micromol/L). CONCLUSION: The sympathetic and purinergic contractile responses can be induced by 2 Hz stimulation, and ATP is the sole transmitter causing the vasoconstriction in the rabbit saphenous artery. Contractile responses to higher frequencies are related to both norepinephrine and ATP. Desensitization of the P2X1 receptor with alpha,beta-methylene ATP potentiates the vascular responses to electric stimulation via a presynaptic mechanism.

Adenosine Triphosphate↗

PubMed2000

Urethane-induced hyperglycemia.

AIM: To study the effects of urethane, at anesthetic dose, on the blood glucose levels in normal rats and hyperglycemic rats, and its effects on the hypoglycemic action of exogenous insulin in alloxan-treated rats. METHODS: Blood glucose concentration was measured with the glucose oxidase method. RESULTS: Urethane at anesthetic dose 1.5 g.kg-1 increased the blood glucose levels in fasting (to 2.6 +/- 0.3 g.L-1, P < 0.01) or glucose-loaded (to 3.9 +/- 0.4 g.L-1, P < 0.01) rats. It did not modify the hyperglycemia induced by epinephrine (normal islet beta-cells) or alloxan (impaired islet beta-cells). In the rats treated with alloxan, blood glucose level decreased to 1.8 +/- 0.7 g.L-1 at 200 min after administration of insulin from control level of 7.0 +/- 2.3 g.L-1, but the hypoglycemic action of exogenous insulin was abolished by urethane. CONCLUSION: Hyperglycemic action of urethane was due to its inhibiting effect on the hypoglycemic effect of insulin, except for its known mechanism of increased sympathetic release.

Alloxan↗

PubMed1999

Selective effects of alfuzosin and doxazosin with intraduodenal administration on urethral pressure of cats.

AIM: To observe the selective effects of alfuzosin (Alf) and doxazosin (Dox) on the urethral pressure by different administration routes. METHODS: The urethral pressure of the anesthetized cat was increased by electric stimulation of the hypogastric nerve. The different effects of Alf or Dox on the arterial blood pressure and urethral pressure between intraduodenal administration (i.d.) and intravenous infusion (i.v.) were compared. RESULTS: When the hypogastric nerve was stimulated by electric stimulation (10 Hz, 25 V), the ratios of ED20(BP)/ED50(UP) i.d. to ED20(BP)/ED50(UP) i.v. were 10.9:4.3 for Alf, and 3.1:2.1 for Dox. The reduction in urethral pressure induced by i.d. Alf was greater than that by i.v. Alf. Dox did not show any difference in its effects by 2 administration routes. CONCLUSION: Intraduodenal administration of Alf, but not Dox, selectively decreased the urethral pressure elevated by electric stimulation. The uroselectivity of i.d. Alf was not due to the species difference in its bioavailability and biotransformation.

Adrenergic alpha-Antagonists↗

PubMed1998

Extraction of sp18 family membrane proteins on posterior head of bull sperm and the effect of anti-sp18 IgG on sperm motility and murine in vitro fertilization.

Bovine sperm heads were separated via ultrasonic treatment and centrifugation. Anti-bull sperm IgG was produced by immunizing rabbits with acrosome-reacted bull sperm heads. SDS PAGE patterns revealed that the main membrane proteins on acrosome-reacted bull sperm head were sp18 family, including 18, 16, and 14 kD, which represented about 64% of the total membrane proteins in bull sperm. Indirect immunofluorescence shown sp18 antigens primarily distributed in postacrosomal and proximal tail regions. Western blot analysis revealed that the anti-bull sperm IgG reacted with sp18 antigens in acrosome-reacted bull sperm head and bull seminal plasma. Anti-bull sperm IgG also reacted with 14, 16, 18, 42, 57 and 60 kD proteins in fresh bull, mouse and rabbit sperm. Anti-sp18 IgG caused agglutination of bull and rabbit sperm, but had no effect on murine sperm. In murine in vitro fertilization trials, preincubating capacitated sperm with 0.364 mg/ml of anti-sp18 IgG resulted in a decrease in the fertilization rate from 75.6% in the controls to 50.8% in the experimental groups (p < 0.001).

Acrosome↗

PubMed1997

Prominent sympathetic purinergic vasoconstriction in the rabbit splenic artery: potentiation by 2,2'-pyridylisatogen tosylate.

1. Vasoconstrictions induced by transmural electrical field stimulation were frequency-dependent from 2 to 32 Hz in the rabbit isolated splenic artery. All contractions were abolished in the presence of tetrodotoxin 1 microM or guanethidine 100 microM. Stimulation at a frequency of more than 32 Hz induced both neurogenic and myogenic responses. 2. Prazosin (1 microM) did not significantly affect vascular contractions to electrical stimulation. Desensitization of P2X-purinoceptors with alpha, beta-methylene ATP (alpha, beta-meATP, 3 microM) abolished the contractions to stimulation at 2-8 Hz and inhibited more than 80% of the vascular response at 16 Hz, but it did not significantly change the responses at 32 Hz. Contractile responses at 32 Hz were inhibited by a combination of prazosin and alpha, beta-meATP. Effects of pyridoxal-phosphate-6-azophenyl-2', 4'-disulphonic acid tetrasodium salt (a selective P2X-purinoceptor antagonist) and suramin (a competitive P2-purinoceptor antagonist) on the neurogenic responses were investigated in this study. 3. 2,2'-Pyridylisatogen tosylate (PIT, 0.3-3 microM) significantly potentiated the vasoconstrictions to electrical stimulation at 2-32 Hz in a concentration-dependent manner. Potentiated responses were restored to the control level 30 min after washing. Concentration-dependent response curves for noradrenaline (NA) or alpha, beta-meATP were not significantly changed by 3 microM PIT, and vasoconstriction by adenosine 5'-triphosphate (ATP, 300 microM) was unaffected by PIT. Coomassie brilliant blue-G (1 microM), which shares the potentiating effect on a recombinant P2Y-purinoceptor with PIT (King et al., 1996), did not inhibit or potentiate the purinergically-mediated component of the response to sympathetic nerve stimulation. The selective alpha 2-adrenoceptor antagonist yohimbine (1 microM) also potentiated the vascular responses to electrical stimulation. 4. The present results indicate that ATP evokes postjunctional contractile responses at low and high frequency electrical stimulation of sympathetic nerves supplying the rabbit splenic artery. PIT potentiates the responses to sympathetic (purinergic) nerve stimulation; this appears to be mainly via prejunctional rather than postjunctional actions.

Adenosine Triphosphate↗

PubMed1996

Developmental changes in sympathetic contraction of the circular muscle layer in the guinea-pig vas deferens.

Contractile responses of the circular muscle of the isolated vas deferens to electrical stimulation (10-80 Hz) and to noradrenaline significantly decreased with increasing age in 3-week-, 10-week- and 18-month-old guinea pigs, observed by the cannula insertion method. There were no significant differences in the contractile responses induced by alpha,beta-methylene ATP or BaCl2 between 3 and 10 weeks old, but the responses to alpha,beta-methylene ATP or BaCl2 decreased in 18-month-old guinea pigs. The contractile response to electrical stimulation was monophasic in 3-week-old guinea pigs, a small portion of which remained after the treatment with prazosin. Desensitisation of P2X-purinoceptors with alpha,beta-methylene ATP significantly inhibited the contractile responses to stimulation with relatively low frequencies, and the combination of both prazosin and alpha,beta-methylene ATP abolished the stimulation-induced contractions. In 10-week- and 18-month-old guinea pigs electrical stimulation evoked a transient contraction followed by a second contraction at the offset of the stimulation (the after-response). The after-responses were blocked by prazosin. These results show that the dominant component of sympathetic cotransmission is noradrenaline; a purinergic component also exists in the sympathetic contraction in the circular muscle of the vas deferens in young guinea pigs, but is virtually absent in the later stages of development. The sympathetic contractions of the circular muscles significantly decrease with increasing age and this appears to be due to changes in postjunctional, rather than prejunctional, mechanisms.

Adenosine Triphosphate↗

PubMed1996

Purinergic and adrenergic transmission and their presynaptic modulation in canine isolated perfused splenic arteries.

Vasoconstrictions induced by periarterial electrical stimulation were analysed pharmacologically in the canine isolated perfused splenic artery. Phentolamine enhanced the vasoconstrictions at 1 Hz but inhibited those at 10 Hz. Suramin and P2x purinoceptor desensitization with alpha,beta-methylene ATP abolished the phentolamine-enhanced and -resistant vasoconstrictions. alpha,beta-Methylene ATP inhibited the vasoconstrictions at 1 Hz and by exogenous ATP but did not change those at 10 Hz and by exogenous noradrenaline. Suramin reduced the vasoconstrictions by the electrical stimulations and alpha,beta-methylene ATP but did not affect those by exogenous ATP. Prazosin did not affect the vasoconstrictions at 1 Hz but inhibited those at 10 Hz. Rauwolscine enhanced the prazosin-resistant vasoconstrictions. These results suggest that the electrical stimulation at 1 Hz releases purinergic transmitters (ATP or a closely related compound) as a dominant candidate for the vasoconstrictions, and a co-released noradrenaline may inhibit the release of purinergic transmitters through presynaptic alpha 2-adrenoceptors in the canine splenic artery.

Adenosine Triphosphate↗

PubMed1995

D-1 dopamine receptors mediate dopamine-induced pancreatic exocrine secretion in anesthetized dogs.

Characterization of dopamine (DA) receptor subtypes was examined on the canine exocrine pancreas using selective DA receptor agonists and antagonists in anesthetized dogs. Each drug was injected i.a. in a single bolus fashion. Graded doses of DA (0.01-3 mumol) produced dose-dependent increases in the secretory rate of pancreatic juice, with a maximum effect at approximately 1 mumol. SCH23390 (3-30 nmol), a selective D-1 DA receptor antagonist, caused a progressive parallel shift to the right in the dose-response curve for DA-induced pancreatic secretion without changes in the maximal response. However, domperidone (3 mumol), a selective D-2 DA receptor antagonist, did not antagonize the DA-induced pancreatic exocrine secretion. A Schild analysis of the data indicates that the inhibitory constant value for SCH23390 to inhibit DA-stimulated secretion was 6.9 nmol. In addition, the stimulatory effects of SKF38393 (0.1-10 mumol) and YM435 (0.3-30 nmol), selective D-1 DA receptor agonists, and LY171555 (1-10 mumol), a selective D-2 DA receptor agonist, on pancreatic secretion were demonstrated. The rank order of agonist potency was YM435 > DA > SKF38393 >> LY171555. These results suggest that DA-induced pancreatic exocrine secretion is mediated by activation of D-1 DA receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1994

Effects of cyclic nucleotide phosphodiesterase IV inhibitor, Ro20,1724, on pancreatic exocrine secretion in dog.

1. The effects of the cyclic nucleotide phosphodiesterase (PDE) inhibitors, Ro20,1724, 3-isobutyl-1-methylxanthine (IBMX), trifluoperazine (TFP) and amrinone on pancreatic exocrine secretion were investigated in anaesthetized dogs in comparison with those of secretion and cholecystokinin octapeptide (CCK-8). 2. Ro20,1724 (1-30 nmol/kg), IBMX (3-30 nmol/kg), secretin (0.01-0.1 pmol/kg) or CCK-8 (0.1-1 pmol/kg) injected i.a. elicited a dose-dependent increase in the secretion of pancreatic juice, but TFP and amrinone (up to 1 mumol/kg) did not. 3. The bicarbonate concentration in pancreatic juice was increased and the protein concentration was decreased by Ro20,1724, IBMX and secretin. Cholecystokinin octapeptide increased the protein concentration but did not alter the bicarbonate concentration. 4. Ro20,1724 and IBMX elicited more than the respective additive secretory response when added together with secretin, although the stimulatory effects of CCK-8 with Ro20,1724 and IBMX were additive. 5. Ro20,1724 and IBMX increased cyclic AMP concentration but did not affect cyclic GMP concentration. 6. These results suggest that Ro20,1724 and IBMX have secretory properties on pancreatic exocrine glands of the dog, which may be mediated through an increase in cyclic AMP subsequent to inhibition of PDE activity. Furthermore, pancreatic PDE enzymes in the dog may be mainly type IV.

1-Methyl-3-isobutylxanthine↗

PubMed1994

Differential effects of omega-conotoxin GVIA and tetrodotoxin on vasoconstrictions evoked by electrical stimulation and nicotinic receptor stimulation in canine isolated, perfused splenic arteries.

1. The effects of omega-conotoxin GVIA (omega-CgTX) and tetrodotoxin (TTX) on vasoconstrictions induced by acetylcholine (ACh) and nicotine were investigated and compared with those induced by periarterial electrical stimulation in the isolated and perfused canine splenic arteries. 2. ACh and nicotine at doses of 0.01 to 1 mumol constricted the splenic artery, dose-dependently. ACh induced consistent responses, but the vasoconstrictor responses to nicotine became significantly smaller with repeated administration of nicotine. 3. Periarterial electrical stimulation produced a vasoconstriction that was abolished by either TTX (30 nmol) or omega-CgTX (3 nmol), but the vasoconstrictor response to nicotine was not significantly affected by the same doses of TTX and omega-CgTX. Inhibitions by TTX and omega-CgTX of ACh-induced vasoconstrictions were small but statistically significant, showing that the percentage inhibition was less than 15%. TTX and omega-CgTX did not affect the vasoconstrictor responses to exogenous noradrenaline (NA). 4. ACh did not produce any vasoconstriction in the preparations treated either with alpha-adrenoceptor antagonists (10 microM bunazosin and 10 microM midaglizole) or with 30 microM guanethidine. NA-induced responses were abolished by alpha-adrenoceptor antagonists, but not affected by guanethidine treatment. 5. Vascular responses to ACh were completely inhibited by 1 mumol hexamethonium. In the preparations treated with 100 nmol nicotine, ACh did not produce any vasoconstriction. However, the NA-induced vasoconstriction was affected by neither hexamethonium nor nicotine treatment. 6. Atropine (1 microM) significantly inhibited but did not abolish the vasoconstrictor responses to ACh. The vascular responses to nicotine and NA were also significantly inhibited by atropine treatment. 7. These results indicate that (1) ACh constricts the splenic artery through the activation of presynaptic nicotinic receptors present on the sympathetic nerves; (2) differential effects of TTX and omega-CgTX on the vascular responses to ACh and nicotine, and to electrical stimulation suggest that the receptor-operated ion channels are mainly responsible for NA release induced by nicotinic receptor stimulation, but N-type VOCCs are responsible for that by electrical stimulation; (3) atropine may have an inhibitory action on nicotine-related responses, in addition to its inhibitory action on NA.

Acetylcholine↗

PubMed1994

Characteristics of the responses of isolated and perfused canine splenic arteries to vasoactive substances and to periarterially electrical stimulation.

Pharmacological characteristics of the canine isolated splenic artery were investigated by the cannula insertion method for observing vascular responses to vasoactive agents and periarterial nerve stimulation. Four alpha-adrenoceptor agonists and tyramine induced vasoconstrictions in a dose-dependent manner, and the order of potency was noradrenaline (NA) > phenylephrine > clonidine > methoxamine > tyramine. Xylazine (a selective alpha 2-adrenoceptor agonist) did not elicit any vasoconstriction. Several autacoids and KCl also constricted the splenic artery dose-dependently, and the order of potency was 5-hydroxytryptamine (5-HT) >> ATP = histamine >> KCl. The dose-response curves for clonidine and NA were shifted to the right by bunazosin (a selective alpha 1-adrenoceptor antagonist), but were not affected by midaglizole (a selective alpha 2-adrenoceptor antagonist). The parameters of electrical stimulation to elicit a clear and constant vasoconstriction were 0.2 msec of pulse duration, 6 V and 0.1 Hz. The vasoconstrictive responses to electrical stimulation at 6-12 V, 0.1-10 Hz and 0.2-1 msec of pulse duration were completely inhibited by tetrodotoxin (TTX) and strongly inhibited by guanethidine. The results in this study suggest that: 1) in contrast with other regional arteries, the canine splenic artery has an alpha 1-adrenoceptor-related and clonidine-sensitive vasoconstrictive response, 2) this artery has no functional postsynaptic alpha 2-adrenoceptors, 3) it may be easier to observe the vascular responses to vasoactive agents in the isolated and perfused arterial segments, and 4) the isolated and perfused canine splenic artery is useful as a preparation to study the sympathetic nerve transmission.

Adrenergic alpha-Agonists↗

PubMed1993

Effects of KRN2391, a novel vasodilator, on pancreatic exocrine secretion in anesthetized dogs.

The effects of KRN2391, a newly synthesized vasodilator, on pancreatic exocrine secretion in anesthetized dogs were compared with those of Ki3315, pinacidil and nitroprusside. Graded doses of KRN2391 (0.03-3 mumol/kg) and nitroprusside (0.003-0.3 mumol/kg) injected i.a. produced dose-dependent increases in the secretion of pancreatic juice, with a high concentration of protein and low concentration of bicarbonate, but Ki3315 or pinacidil did not (up to 10 mumol/kg). KRN2391 and nitroprusside increased the cyclic GMP levels in pancreatic tissue together with the increase in pancreatic secretion. Methylene blue decreased pancreatic secretion and cyclic GMP levels stimulated by KRN2391 and nitroprusside, but glibenclamide did not. KRN2391, Ki3315, pinacidil and nitroprusside caused vasodilator actions. These results suggest that KRN2391 has direct secretory properties on pancreatic exocrine glands of the dog and its nitro moiety has an important role in the stimulation of pancreatic secretion, but the K+ channel opening action or increasing of blood flow rate does not participate in the secretion.

Animals↗

PubMed1993

Dual actions of glucagon: direct stimulation and indirect inhibition of dog pancreatic secretion.

The secretory actions of glucagon on the exocrine pancreas were examined using two kinds of canine preparations. In the isolated and blood-perfused dog pancreas with venous drainage, i.a. injection of glucagon did not inhibit secretin/cholecystokinin-octapeptide (CCK-8)-stimulated pancreatic secretion, but instead dose dependently enhanced both basal and stimulated pancreatic secretion. Glucagon-induced increase of pancreatic secretion was potentiated by 3-isobutyl-1-methylxanthine. In contrast, i.v. bolus injection of glucagon (3 and 10 nmol/kg) first augmented transiently then suppressed secretin/CCK-8-stimulated pancreatic secretion while simultaneously increasing circulating plasma somatostatin immunoreactivity from 14.2 to 214 fmol/ml in anesthetized intact dogs. The inhibition of secretin/CCK-8-stimulated pancreatic secretion and elevation of plasma somatostatin immunoreactivity induced by glucagon were comparable with those due to somatostatin-14. Thus, these results indicate that glucagon stimulates pancreatic secretion directly; the inhibitory action of glucagon is indirect and appears to be related to a rise in the circulating level of somatostatin immunoreactivity.

1-Methyl-3-isobutylxanthine↗

PubMed1993

Positive chronotropic and inotropic responses to BRL 37344, a beta 3-adrenoceptor agonist in isolated, blood-perfused dog atria.

We investigated the chronotropic and inotropic responses to BRL 37344 (a beta 3-adrenoceptor agonist) and isoproterenol in isolated, blood-perfused dog atria. BRL 37344 (0.1-30 nmol) or isoproterenol (0.001-0.3 nmol) increased the sinus rate and contractile force dose dependently. BRL 37344 was 290 times less potent than isoproterenol to increase sinus rate and 140 times less potent to increase atrial force. Both propranolol and bisoprolol similarly inhibited the positive chronotropic and inotropic responses to BRL 37344 and isoproterenol dose dependently. ICI 118,551 (0.1 and 1 nmol) did not significantly affect the positive cardiac responses to BRL 37344 or isoproterenol. Neither imipramine nor tetrodotoxin significantly affected the positive cardiac responses to BRL 37344. These results suggest that the positive chronotropic and inotropic responses to BRL 37344 are mediated mainly by beta 1-adrenoceptors in the dog heart. It is unlikely that beta 3-adrenoceptors, as previously reported in adipose tissue or gastrointestinal smooth muscle, mediate chronotropic and inotropic responses in the normal dog heart.

Adrenergic beta-Agonists↗

PubMed1993

Muscarinic receptor subtypes mediating vasodilation and vasoconstriction in isolated, perfused simian coronary arteries.

Using the cannula insertion method, we investigated the vascular responses of isolated simian coronary artery to acetylcholine (ACh). When the preparation was partially precontracted by 20 mM KCl, ACh and carbachol induced vasodilation dose dependently in coronary artery with endothelium, but ACh and carbachol contracted the coronary artery after removal of the endothelium by 1 mg saponin. A selective M1 receptor agonist 4-[N-(3-chlorophenyl)carbamoyloxy]-2-butinyltrimethylammonium++ + chloride (McN-A-343) did not affect the perfusion pressure of the precontracted coronary arteries significantly. Both these responses to ACh were inhibited by the M3 receptor antagonist 4-dipheny-lacetoxy N-methylpiperidine methobromide (4-DAMP) in a dose-dependent manner, but not by a selective M2 receptor antagonist AF-DX 116 (11-[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzo-diazepine-6-one). A selective M1 receptor antagonist pirenzepine did not affect ACh-induced vasoconstriction significantly and inhibited the vasodilation partially only at the highest dose (100 nmol). The effects of three antagonists on the vasodilative responses to carbachol were also studied and almost the same results were observed. Removal of the endothelium did not affect sodium nitroprusside (SNP)-induced vasodilation significantly. Pirenzepine, AF-DX 116, and 4-DAMP did not affect the action of isoproterenol. These data suggest that the vasodilation elicited by ACh is mediated by release of endothelium-derived relaxing factors (EDRF) consequent to the activation of M3 receptors on endothelial cells, and the constriction is mediated by stimulation of M3 receptors on smooth muscle cells in isolated simian coronary arteries.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

PubMed1993

Inhibition by omega-conotoxin GVIA of the chronotropic responses to sympathetic and parasympathetic nerve stimulation in the isolated, blood-perfused atrium of the dog.

1. We investigated the effects of omega-conotoxin GVIA (omega-CgTX), a blocker of N-type voltage-operated calcium channels, on the chronotropic response to stimulation of the intracardiac sympathetic and parasympathetic nerves in the isolated, blood-perfused right atrium of the dog. 2. omega-CgTX (0.3-3 nmol) itself did not affect the sinus rate significantly, but it inhibited the negative followed by positive chronotropic response to simultaneous stimulation of sympathetic and parasympathetic nerves in a dose-dependent manner. 3. omega-CgTX at higher doses (1-3 nmol) inhibited the positive response to sympathetic stimulation more strongly than the negative response to parasympathetic stimulation. omega-CgTX (3 nmol) abolished the positive chronotropic response to sympathetic nerve stimulation in the atrium treated with atropine, but did not abolish the negative response to selective parasympathetic stimulation. Neither the chronotropic response to noradrenaline nor the response to acetylcholine was affected by omega-CgTX. 4. These results indicate that omega-CgTX inhibits not only the response to sympathetic stimulation but also the response to parasympathetic stimulation in the dog heart and it inhibits the positive chronotropic response to sympathetic stimulation more strongly than the negative chronotropic response to parasympathetic stimulation.

Acetylcholine↗

PubMed1992

Cardiac electrical responses to catecholamines are differentially mediated by beta 2-adrenoceptors in anesthetized dogs.

We investigated the beta 2-adrenoceptor-mediated effects of atrial and ventricular effective refractory period (ERP), SA node pacemaker activity, and AV conductivity induced by sympathetic nerve stimulation or epinephrine infusion in anesthetized dogs. A beta 2-adrenoceptor antagonist, ICI 118,551 up to 100 micrograms/kg, i.v., inhibited the positive chronotropic and dromotropic responses to sympathetic stimulation but did not shorten the atrial or ventricular ERP, ICI 118,551 also attenuated the positive chronotropic and dromotropic responses and the shortening of atrial ERP in response to epinephrine but not the shortening of ventricular ERP. A selective beta 1-adrenoceptor antagonist, atenolol, inhibited each electrical cardiac response to sympathetic stimulation and epinephrine infusion in a similar manner. These results suggest that beta 2-adrenoceptor-mediated electrical cardiac responses to endogenous catecholamines also exist in addition to the predominant beta 1-adrenoceptor-mediated responses, and that the order of the proportion of beta 2-adrenoceptor-mediated cardiac effects was SA node pacemaker activity much greater than AV conductivity = atrial ERP much greater than ventricular ERP in the dog heart.

Anesthesia↗