Biomedical subjects

C C Pang

Publications and source records attributed to C C Pang.

At least 19 recordsLinked to original sources

PubMed1995

Regional haemodynamic effects of platelet activating factor in the rat.

The effects of platelet activating factor (PAF) on haemodynamics in the absence and presence of the potent PAF receptor antagonist TCV-309 (3-bromo-5-[N-phenyl-N-[2-[[2-(1,2,3,4-tetrahydro-2- isoquinolyl-carbonyloxy)ethyl]carbamoyl]ethyl]carbamoyl]-1- propylpyridinium nitrate) were studied by the microsphere technique in pentobarbitone-anaesthetized rats. I.v. infusion of the low dose PAF (0.05 microgram kg-1 min-1) did not significantly alter mean arterial pressure, cardiac output or total peripheral resistance but increased arterial conductances in the stomach, intestine, caecum and colon and reduced conductance in the spleen. I.v. infusion of the high dose of PAF (0.3 microgram kg-1 min-1) markedly reduced mean arterial pressure (-53 mm Hg) and cardiac output (-62%) and insignificantly increased total peripheral resistance. Arterial conductances in the lungs, stomach, intestine, caecum and colon, kidneys and spleen were reduced and those in the heart and muscle were increased. TCV-309 (10 micrograms kg-1) abolished all changes in arterial pressure, cardiac output and total peripheral resistance and arterial conductances elicited by either the low or the high dose of PAF. The results show that a non-hypotensive dose of PAF caused vasodilatation of the gastrointestinal organs and vasoconstriction of the spleen. A high dose of PAF which markedly decreased arterial pressure and cardiac output caused vasodilatation of the heart and muscle and vasoconstriction of the lungs (bronchial), gastrointestinal organs, kidneys and spleen. All haemodynamic changes were blocked by TCV-309 indicating the involvement of PAF receptors.

Animals↗

PubMed1995

Increase by NG-nitro-L-arginine methyl ester (L-NAME) of resistance to venous return in rats.

1. The effects of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on mean circulatory filling pressure (MCFP), total peripheral resistance (TPR), cardiac output (CO) and resistance to venous return (Rv) were studied in rats. 2. In conscious, unrestrained rats, L-NAME (0.5-16 mg kg-1) dose-dependently increased mean arterial pressure (MAP) but not MCFP, an inverse index of venous compliance, either in the absence or presence of the ganglionic blocker mecamylamine (10 mg kg-1). 3. In pentobarbitone-anaesthetized rats, L-NAME (2, 4, 8 mg kg-1) increased MAP and reduced CO in a dose-related manner but did not change MCFP, TPR (+84, +140 and +192%) as well as Rv (+62, +72, +110%) were dose-dependently increased by L-NAME. 4. Our results show that L-NAME reduces CO by increasing arterial as well as venous resistances. L-NAME does not affect MCFP.

Amino Acid Oxidoreductases↗

PubMed1995

Vascular pharmacology of methylene blue in vitro and in vivo: a comparison with NG-nitro-L-arginine and diphenyleneiodonium.

1. The vascular effects of the soluble guanylyl cyclase inhibitor, methylene blue as well as the nitric oxide (NO) synthase inhibitors, NG-nitro-L-arginine (L-NOARG) and diphenyleneiodonium (DPI) were studied in rat isolated aortic rings and conscious, unrestrained rats. 2. Acetylcholine (ACh) and sodium nitroprusside (SNP) caused concentration-dependent relaxation of preconstricted aortic rings. Both methylene blue (1 x 10(-5) M) and L-NOARG (3 x 10(-5) M) abolished ACh-induced relaxation; however, methylene blue but not L-NOARG shifted the concentration-response curve of SNP to the right. 3. In conscious rats, i.v. infusion of methylene blue (1.1 x 10(-5) mol kg-1 min-1), at a concentration which reduced the aortic tissue level of cyclic GMP by 50%, did not significantly alter mean arterial pressure (MAP) and heart rate (HR). In contrast, i.v. bolus injection of L-NOARG (1.5 x 10(-4) mol kg-1) markedly increased MAP and decreased HR. 4. Both ACh and SNP dose-dependently decreased MAP in conscious rats. Methylene blue did not alter the magnitude or duration of ACh- or SNP-induced depressor responses. L-NOARG, on the other hand, significantly though incompletely, reduced the magnitude and duration of the depressor response to ACh but not SNP. The depressor response to ACh or SNP was not altered by pretreatment with indomethacin (1.4 x 10(-5) mol kg-1) or capsaicin (3.3 x 10(-4) mol kg-1). 5. NG-nitro-L-arginine methyl ester (L-NAME) also caused dose-dependent increases in MAP in conscious rats. Both methylene blue and DPI (1 x 10-5 mol kg-1) selectively shifted the dose-pressor response curve of L-NAME to the right.6. These results suggest that: (1) the inhibition of endogenous NO biosynthesis does not necessarily lead to pressor response in vivo, (2) L-NOARG may not produce pressor response solely via the inhibition of endogenous endothelial NO biosynthesis, and (3) the depressor responses to ACh and SNP may not involve the release of NO or prostanoids or afferent nerve transmitters.

Acetylcholine↗

PubMed1995

Effects of calcitonin gene-related peptide receptor antagonists on renal actions of adrenomedullin.

1. Adrenomedullin is a novel vasoactive peptide which is produced in the lungs, ventricle, kidneys, heart and adrenal medulla. Adrenomedullin shows homology to calcitonin gene-related peptide (CGRP) and has similar pharmacological actions to CGRP. 2. This study examined the dose-response effects of adrenomedullin (rat, 11-50) on mean arterial pressure (MAP), heart rate (HR), renal blood flow (RBF), glomerular filtration rate (GFR) and renal tubular electrolyte excretion in Inactin-anaesthetized Sprague Dawley rats. The possible involvement of CGRP receptors in actions of adrenomedullin was also examined via renal arterial injection of a CGRP receptor antagonist, CGRP (8-37) (1 or 10 nmol kg-1) or [Tyr0]CGRP(28-37) (3 or 30 nmol kg-1), starting 15 min prior to the administration of adrenomedullin. 3. Renal arterial infusion (0.001 to 1 nmol kg-1) of adrenomedullin did not alter MAP, HR and renal K+ excretion but dose-dependently increased RBF and arterial conductance, GFR, urine flow and Na+ excretion. 4. The renal actions of adrenomedullin were not blocked by either the low or the high dose of CGRP(8-37) or [Tyr0]CGRP(28-37). 5. The results show that adrenomedullin causes renal vasodilatation, increments in GFR, diuresis and natriuresis. The renal actions of adrenomedullin are not mediated via the activation of CGRP1 receptors.

Adrenomedullin↗

PubMed1995

Renal vascular and tubular actions of calcitonin gene-related peptide: effect of NG-nitro-L-arginine methyl ester.

The existence of calcitonin gene-related peptide (CGRP) nerve fibers and CGRP receptors in the kidney and the coupling of the receptors to adenylyl cyclase suggest that CGRP participates in renal regulation. This study investigates the dose-effect relationship of CGRP on renal blood flow (RBF) and arterial conductance, glomerular filtration rate (GFR) and tubular excretion in Inactin-anesthetized, Sprague-Dawley rats. The contributions of endothelium-derived relaxing factor/nitric oxide in the renal actions of CGRP also were investigated via renal arterial injection of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 0.5 or 5 mg/kg). Renal arterial infusion of CGRP (0.3-300 pmol/kg/min) did not affect mean arterial pressure or heart rate. Low doses of CGRP increased RBF, arterial conductance and GFR, but the highest dose reduced RBF and conductance without affecting GFR. High doses of CGRP also increased urine flow and excretions of Na+ and K+. The renal vasodilator but not the constrictor effect of CGRP was inhibited by both doses of L-NAME. The increase in GFR by the lowest dose of CGRP was attenuated by the low dose and abolished by the high dose of L-NAME. L-NAME did not inhibit the diuretic, natriuretic and kaliuretic effects elicited by high doses of CGRP. The results show that a low dose of CGRP causes renal vasodilatation via the release of endothelium-derived relaxing factor/nitric acid.

Animals↗

PubMed1994

NG-nitro-L-arginine contracts vascular smooth muscle by an endothelium-independent mechanism.

We characterized the contractile effect of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) in endothelium-denuded rat aortic rings. Incubation with L-NNA (4 x 10(-6)-6.4 x 10(-5) M) for 5 h dose-dependently contracted endothelium-denuded aortic rings. In contrast, incubation with NG-nitro-D-arginine (D-NNA 6 x 10(-6)-4 x 10(-4) M), diphenyleneiodonium (DPI, NO synthase inhibitor, 3.2 x 10(-6) M) or dexamethasone (10(-7) M, inhibitor of expression of inducible NO synthase) did not contract the denuded rings. The L-NNA-induced contraction was not significantly altered by the presence of the endothelium or by pretreatment with L-arginine (L-Arg 2 x 10(-3) M) or lipopolysaccharide (100 ng/ml). These results suggest that L-NNA causes slow contraction of endothelium-denuded vascular smooth muscle (VSM) by a mechanism independent of the inhibition of constitutive or inducible NO biosynthesis.

Animals↗

PubMed1994

Alpha 1b-adrenoceptors mediate renal tubular sodium and water reabsorption in the rat.

1. It is known that activation of alpha 1-adrenoceptors causes renal vasoconstriction and increased tubular Na+ and water reabsorption, with the alpha 1a-subtype mediating the constrictor effect. 2. This study examines which subtype of alpha 1-adrenoceptors mediates tubular Na+ and water reabsorption in pentobarbitone-anaesthetized rats. In order to avoid systemic effects, phenylephrine (0.3 to 30 micrograms kg-1), methoxamine (0.1-10 micrograms kg-1) and vehicle were infused into the right renal artery (via the suprarenal artery) of three groups of rats. Two other groups of rats were continuously infused with the irreversible selective alpha 1b-adrenoceptor antagonist, chloroethylclonidine (3 mg kg-1 h-1) for 1 h, prior to the construction of dose-response curves to phenylephrine or methoxamine. Another group was continuously infused with the irreversible selective alpha 1a-adrenoceptor antagonist, SZL-49 (10 micrograms kg-1 h-1) for 1 h, prior to the construction of dose-response curves to phenylephrine. Mean arterial pressure (MAP), heart rate (HR), urine flow, Na+ and K+ excretion, and urine osmolality were monitored. 3. Phenylephrine and methoxamine did not affect MAP or HR but dose-dependently and significantly decreased urine flow, urine osmolality as well as Na+ excretion and, slightly increased K+ excretion, although this was significant only for phenylephrine. 4. The antidiuretic, antinatriuretic and kaliuretic effects of phenylephrine were abolished by pretreatment with chloroethylclonidine, but were not inhibited by SZL-49. The inhibitory effects of methoxamine on urine flow and Na+ excretion were also almost totally abolished by chloroethylclonidine. 5. Our results show that alpha 1b-adrenoceptors mediate renal tubular Na+ and water reabsorption.

Absorption↗

PubMed1993

Inhibitory actions of diphenyleneiodonium on endothelium-dependent vasodilatations in vitro and in vivo.

1. This study examined the in vitro and in vivo inhibitory effects of diphenyleneiodonium (DPI), a novel inhibitor of nitric oxide (NO) synthase, on endothelium-dependent vasodilatations. 2. DPI (3 x 10(-8)-3 x 10(-6) M) concentration-dependently inhibited acetylcholine (ACh)-induced relaxation in preconstricted rat thoracic aortic rings, with an IC50 of 1.8 x 10(-7) M and a maximal inhibition of nearly 100%. DPI (3 x 10(-6) M) also completely inhibited the relaxation induced by the calcium ionophore, A23187 but not by sodium nitroprusside (SNP). The inhibitory effect of DPI (3 x 10(-7) M) on ACh-induced relaxation was prevented by pretreatment with NADPH (5 x 10(-3) M) and FAD (5 x 10(-4) M) but not L-arginine (L-Arg, 2 x 10(-3) M). Pretreatment with NADPH did not alter the inhibitory effect of NG-nitro-L-arginine on ACh-induced relaxation. 3. The inhibitory effect of DPI on ACh-induced relaxation in the aortae lasted > 4 h after washout. In contrast to pretreatment, post-treatment (1 h later) with NADPH (5 x 10(-3) M) reversed only slightly the inhibitory effect of DPI. 4. In conscious rats, DPI (10(-5) mol kg-1) inhibited the depressor response to i.v. infused ACh, but not SNP. However, it caused only a transient pressor response which was previously shown to be due completely to sympathetic activation. 5. Thus, DPI is an efficacious and 'irreversible' inhibitor of endothelium-dependent vasodilatation in vivo and in vitro. The mechanism of the inhibition may involve antagonism of the effects of FAD and NADPH, co-factors of NO synthase. However, unlike the N0-substituted arginine analogues (another class of NO synthase inhibitors), DPI-induced suppression of endothelium-dependent vasodilatation in vivo does not lead to a sustained rise in blood pressure.

Acetylcholine↗

PubMed1993

Selective inhibition of pressor and haemodynamic effects of NG-nitro-L-arginine by halothane.

We investigated the characteristics of inhibition by halothane of the pressor responses to NG-substituted L-arginine derivatives, nitric oxide (NO) synthase inhibitors. Intravenous (i.v.) bolus injections of NG-nitro-L-arginine (L-NNA, 1-32 mg/kg), NG-nitro-L-arginine methyl ester (L-NAME, 0.4-12.8 mg/kg), norepinephrine (NE, 0.25-8 micrograms/kg) and angiotensin II (AII, 0.02-0.64 micrograms/kg) each caused dose-dependent pressor responses in conscious rats. Halothane attenuated responses to the highest dose of NE and AII by approximately 18% but completely abolished responses to L-NNA and L-NAME. The haemodynamic effects of L-NNA were further examined by the microsphere technique in two groups of conscious rats and two groups of halothane-anaesthetized rats. An i.v. bolus injection of L-NNA (16 mg/kg) in conscious rats increased mean arterial pressure (MAP) and total peripheral resistance (TPR) and reduced heart rate (HR) and cardiac output (CO). These changes were associated with reduced conductance in all vascular beds, with the greatest reduction in the lungs and the least in the liver. In halothane-anaesthetized rats, L-NNA caused significant but markedly less change in MAP, HR, TPR, and CO as compared with those in conscious rats. The vasoconstrictor effects of L-NNA were attenuated by halothane in all beds except liver and spleen, with the greatest inhibition in heart. Our results suggest that NO plays a role in maintenance of peripheral vascular resistance and that halothane selectively and "noncompetitively" inhibits the vasoconstrictor effects of NO synthase inhibitors.

Amino Acid Oxidoreductases↗

PubMed1993

Functional integrity of the central and sympathetic nervous systems is a prerequisite for pressor and tachycardic effects of diphenyleneiodonium, a novel inhibitor of nitric oxide synthase.

The pressor and tachycardic effects of diphenyleneiodonium (DPI), a novel inhibitor of endothelial nitric oxide synthase with chemical structure different from those of NG-substituted Arg analogs, were studied in pentobarbital-anesthetized rats. Bolus injections of DPI (0.05-1.6 mg/kg i.v.) caused transient (1-2 min in duration) and dose-dependent increases in mean arterial pressure (MAP) with ED50 of 0.22 +/- 0.02 mg/kg and maximum effect (Emax) of 58 +/- 3 mm Hg, and heart rate (HR) with ED50 of 0.26 +/- 0.03 mg/kg and Emax of 60 +/- 5 beats/min. Pretreatments with tetrodotoxin, reserpine, guanethidine, mecamylamine, but not atropine, rauwolscine, captopril nor L-Arg, attenuated the MAP and HR responses to DPI. Phentolamine and prazosin attenuated the MAP but not HR response whereas propranolol attenuated the HR but not MAP response of DPI. Pithing abolished, whereas spinal cord transection reduced, the MAP and HR responses to DPI. Pithing did not alter the pressor response but blocked the reflex bradycardic response to NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase. Bolus injection of a single dose of DPI (1.6 mg/kg i.v.) or NG-nitro-L-arginine increased MAP, but only DPI caused immediate and large increases (> 1 ng/ml) in plasma norepinephrine, epinephrine and moderate increase in dopamine; pretreatment with reserpine attenuated, whereas pithing abolished these increases. The increases in plasma norepinephrine and epinephrine by DPI were positively correlated to increases in MAP and HR. The results demonstrate that DPI, unlike NG-substituted Arg analogs, produces pressor and tachycardic effects via indirect activation of the sympathetic nervous system.

Amino Acid Oxidoreductases↗

PubMed1992

Direct and indirect effects of angiotensin II on venous tone in conscious rats.

The direct and indirect effects of angiotensin II (ANGII) on mean arterial pressure (MAP) and mean circulatory filling pressure (MCFP), an index of body venous tone, were investigated in conscious rats. Dose-response curves of ANGII were constructed in control rats (Group I), rats pretreated with saralasin (competitive ANGII antagonist, Group II), with guanethidine (inhibitor of sympathetic postganglionic neurons. Group III), or the ganglionic blocker hexamethonium (Group IV) and rats given unilateral right adrenalectomy two days prior to the study (Group V). The infusion of single doses of ANGII in control, adrenalectomized, guanethidine-treated and hexamethonium-treated rats dose dependently increased MAP to similar maxima; ED50 value was increased by adrenalectomy but unaffected by guanethidine nor hexamethonium. The pressor effects of ANGII was almost completely abolished by saralasin. ANGII dose dependently increased MCFP in control rats. In hexamethonium-treated rats, ANGII also dose relatedly increased MCFP which reached similar maximum as that in control rats, but the ED50 value was reduced. Saralasin almost completely abolished the MCFP response. Both guanethidine and adrenalectomy reduced maximum MCFP response to ANGII, but neither altered the ED50 value. Our results show that the sympathetic nervous system contributed greater to the MCFP than MAP effects of ANGII. Both direct and indirect effects of ANGII are mediated via the activation of ANGII receptors that are susceptible to blockade by saralasin.

Angiotensin II↗

PubMed1992

Calcitonin gene-related peptide is a venous dilator in conscious rats.

The effect of calcitonin gene-related peptide (CGRP) on body venous tone is not known. This study examines the dose-response effects of rat alpha CGRP on mean circulatory filling pressure (MCFP), an index of body venous tone, in conscious rats. Dose-response curves of CGRP were constructed in three groups of rats, namely, (I) intact, (III) rats pretreated with the ganglionic blocker hexamethonium and (V) rats pretreated with noradrenaline to raise mean arterial pressure (MAP) and MCFP. Three additional groups, (II), (IV) and (VI), served as time controls and were treated similarly to (I), (III) and (V), respectively, except that they were given saline (0.9% NaCl) in place of CGRP. The infusion of CGRP in intact rats dose dependently decreased MAP, increased heart rate (HR) and slightly reduced MCFP. In ganglionic-blocked rats, CGRP caused similar depressor responses but less tachycardia than in intact rats, however, it also slightly reduced MCFP. In rats given noradrenaline, CGRP dose dependently decreased MAP, MCFP and increased HR. The results show that CGRP has venodilator activities; its venous effect is best revealed at elevated venous tone.

Analysis of Variance↗

PubMed1992

Effects of drugs on body venous tone, as reflected by mean circulatory filling pressure.

The venous system is supremely important in the control of cardiac output. Drugs which affect the venous system have profound effects on haemodynamics. This review comments on the methods available for the determination of venous compliance, resistance, and unstressed volume and describes the mean circulatory filling pressure (MCFP) technique, its usefulness and limitations. The MCFP technique involves the measurement of central venous pressure during brief (5-7 s) circulatory arrest. Mathematically, MCFP is inversely proportional to vascular compliance while experimentally, it is a primary determinant of venous return. The MCFP technique provides a reproducible and relatively non-traumatic means for the estimation of body venous tone in conscious and anaesthetised animals. Drugs examined by this technique include alpha and beta adrenoceptor agonists and antagonists, ganglionic blockers, vasoactive peptides (endothelin, vasopressin, angiotensin, neuropeptide Y), and vasodilators (hydralazine, nitroprusside, glyceryl trinitrate, calcium antagonists, and MCI-154).

Animals↗

PubMed1992

Mechanism of the vasodilator action of calcitonin gene-related peptide in conscious rats.

1. The aim of this study was to investigate whether the hypotensive effect of rat alpha-calcitonin gene-related peptide (alpha CGRP) in conscious rats is mediated by endothelium-derived nitric oxide (NO) or the opening of adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels. 2. Dose-mean arterial pressure (MAP)-response curves of alpha CGRP were examined in the presence of vehicle, phenylephrine, KATP channel antagonist glibenclamide or NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and NG-nitro-D-arginine methyl ester (D-NAME). Dose-MAP-response curves for sodium nitroprusside were also constructed in the presence and absence of L-NAME and D-NAME. 3. alpha CGRP and nitroprusside produced dose-dependent reductions in MAP which were potentiated by phenylephrine. Both L-NAME and D-NAME attenuated the depressor response to alpha CGRP but not nitroprusside. 4. Dose-MAP-response curves for pinacidil, a KATP-channel activator, were also examined in the presence of glibenclamide or vehicle. Glibenclamide attenuated pinacidil- but not alpha CGRP-induced reductions in MAP. 5. It is concluded that the hypotensive effects of alpha CGRP are partially mediated via endothelium-derived NO but not via the opening of KATP channels.

Adenosine Triphosphate↗

PubMed1992

Effects of anaesthetic agents on pressor response to beta-blockers in the rat.

It has been shown that paradoxical pressor response to a beta-adrenoceptor antagonist occurs in conscious rats pretreated with an alpha-adrenoceptor antagonist. This study examines the influence of anaesthetic agents on mean arterial pressure (MAP) response to a beta-blocker. Cumulative dose-response curves of propranolol (non-selective), ICI 118,551 (beta 2-selective) and atenolol (beta 1-selective) were constructed in phentolamine-treated rats anaesthetized with urethane, pentobarbitone or halothane. I.v. injections of all three beta-blockers caused dose-dependent increases in MAP in urethane-anaesthetized rats. In halothane-anaesthetized rats, propranolol and atenolol did not alter MAP while ICI 118,551 caused a small dose-dependent increase in MAP. In the presence of pentobarbitone, none of the beta-blockers raised MAP. In the second series of experiments, a single i.v. bolus dose of propranolol was given in phentolamine-treated rats anaesthetized with pentobarbitone, amobarbitone, ketamine or chloralose. Propranolol did not affect MAP in rats anaesthetized with pentobarbitone, amobarbitone and chloralose but it partially reversed the hypotensive effect of phentolamine in ketamine-anaesthetized rats. In the third series, propranolol or atenolol was i.v. injected in pentobarbitone-anaesthetized rats treated with both phentolamine and adrenaline. Both propranolol and atenolol raised MAP. Our results show that anaesthetic agents differentially affect the MAP response to a beta-blocker.

Adrenergic beta-Antagonists↗

PubMed1992

Competitive antagonism of pressor responses to angiotensin II and angiotensin III by the angiotensin II-1 receptor ligand losartan.

Losartan (DuP 753) and PD123177 are nonpeptide angiotensin (ANG) receptor ligands for subtypes of ANG II receptors ANG II-1 and ANG II-2, respectively. We examined the effects of losartan and PD123177 on dose - mean arterial pressure (MAP) response curves for ANG II and ANG III in eight groups (n = 6 each) of conscious rats. Saline (0.9% NaCl), losartan (1 x 10(-6) and 9 x 10(-6) mol/kg), and PD123177 (2 x 10(-5) mol/kg) were i.v. bolus injected 15 min before the construction of ANG II dose - response curves in groups I, II, III, and IV, respectively. Groups V-VIII were treated similarly to I-IV except that ANG III was given in place of ANG II. Losartan dose dependently shifted the dose-response curves of ANG II and ANG III to the right with similar dissociation constants (-log KI of 6.6 +/- 0.7 and 6.6 +/- 0.1 mol/kg, respectively) and no change in the maxima. PD123177 affected neither maximum MAP nor ED50 values for ANG II or ANG III. Our results show that losartan but not PD123177 is a competitive antagonist of the MAP effects of ANG II and ANG III.

Angiotensin II↗

PubMed1992

The sympathetic nervous system facilitates endothelin-1 effects on venous tone.

The effects of endothelin-1 (ET-1) or normal saline (0.9% NaCl) on mean arterial pressure (MAP), heart rate (HR) and mean circulatory filling pressure (MCFP), an index of body venous tone, were studied in 10 groups (n = 6 each) of conscious, unrestrained rats continuously i.v. infused with vehicle, verapamil, both hexamethonium and verapamil, phentolamine or, both phentolamine and verapamil. Infusion (i.v.) of normal saline into the five control groups did not significantly alter MAP, HR or MCFP. Cumulative i.v. bolus of ET-1 (0.8, 1.6, 3.2, 6.4, 12.8 and 19.4 x 10(-10) mol/kg) reduced HR in all five treatment groups and dose-dependently increased MAP in the presence of either vehicle or phentolamine, but did not affect MAP in the groups treated with verapamil. The ability of ET-1 to reduce HR in verapamil-treated rats, despite the absence of a pressor response, suggests that ET-1 is negatively chronotropic. ET-1 alone slightly increased MCFP and it did not alter MCFP in the presence of phentolamine. In the presence of verapamil, ET-1 markedly raised MCFP, and this was abolished by concurrent treatment with either hexamethonium or phentolamine. Therefore, ET-1 markedly elevates venous tone in the presence of verapamil via reflex-mediated increase in sympathetic nerve activity and the activation of alpha adrenoceptors.

Animals↗

PubMed1991

Effects of neuropeptide Y on mean circulatory filling pressure in intact and ganglionic-blocked conscious rats.

The dose-response effects of neuropeptide Y (NPY) and the vehicle, 0.9% NaCl, on mean arterial pressure (MAP), heart rate (HR) and mean circulatory filling pressure (MCFP), an index of body venous tone, were examined in conscious, intact and hexamethonium-treated rats. Saline infusions in intact and hexamethonium-treated rats did not significantly affect MAP, HR and MCFP. The i.v. infusion of NPY in intact rats dose dependently increased MAP, decreased HR, but did not alter MCFP. In the presence of hexamethonium, the pressor effect of NPY was enhanced, the lack of MCFP effect remained and the bradycardic effect was markedly attenuated. Our results suggest that NPY has moderate effects on MAP, but negligible effects on body venous tone.

Animals↗