Biomedical subjects

C C Pang

Publications and source records attributed to C C Pang.

At least 55 records · Page 3Linked to original sources

PubMed1994

Effects of adrenalectomy and chemical sympathectomy on pressor and tachycardic responses to diphenyleneiodonium.

We have reported that diphenyleneiodonium (DPI), a flavoprotein inhibitor, caused pressor and tachycardic responses by indirectly activating the sympathetic nervous system. In this study, bilateral adrenalectomy and chemical sympathectomy by 6-hydroxydopamine (6-OH-DA) were used to examine the contributions of the adrenal medullae and sympathetic nerve terminals to the pressor and tachycardic responses to DPI in pentobarbital-anesthetized rats. Intravenous bolus injections of DPI (0.05-1.6 mg/kg) caused dose-dependent increases in mean arterial pressure and HR. Neither bilateral adrenalectomy nor pretreatment (26 hr earlier) with 6-OH-DA (100 mg/kg, i.p.) significantly affected the dose-MAP curve of DPI, although 6-OH-DA but not adrenalectomy slightly and significantly shifted the dose-HR curve to the right without affecting the maximum. The combination of bilateral adrenalectomy and 6-OH-DA reduced the maximum mean arterial pressure and HR responses to DPI by 71% and 35%, respectively. Intravenous bolus injection of DPI (1.6 mg/kg) caused increases in plasma norepinephrine, epinephrine and dopamine of more than 2, 2 and 0.1 ng/ml, respectively. Although bilateral adrenalectomy reduced the DPI-induced increases of norepinephrine, epinephrine and dopamine by 85%, 100% and 93%, and 6-OH-DA reduced these increases by 67%, 48% and 61%, respectively, the combination of adrenalectomy and 6-OH-DA abolished the increases in catecholamines. These results show that sympathetic nerve terminals and sympathoadrenals play overlapping roles in the pressor and tachycardic responses to DPI, with the adrenal medullae as the primary source of plasma catecholamines released by DPI.

Adrenal Medulla↗

PubMed1993

Endothelium-derived nitric oxide partially mediates salbutamol-induced vasodilatations.

This study examined the ability of salbutamol (selective beta 2-adrenoceptor agonist) to cause endothelium-dependent relaxation in rat aortic rings and depressor response in conscious rats. Salbutamol (0.01-100 microM) concentration dependently relaxed preconstricted aortic rings. The relaxant response was partially attenuated by either mechanical removal of the endothelium or treatment with NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). In conscious rats, either i.v. infused phenylephrine (5 micrograms/kg per min) or i.v. bolus injected L-NAME (12.8 mg/kg), but not the vehicle, caused similar sustained increases in mean arterial pressure (MAP). I.v. infused salbutamol (2-128 micrograms/kg per min, each dose for 5 min) dose dependently decreased MAP in vehicle-treated rats; the depressor responses were potentiated by hypertension induced by phenylephrine. In contrast, the magnitudes of the depressor response to salbutamol in L-NAME-treated rats were less than those in rats pretreated with phenylephrine or the vehicle. I.v. bolus injections of salbutamol (0.25-16 micrograms/kg) also caused dose-dependent and transient decreases in MAP in vehicle-treated rats. The magnitude but not the duration of the depressor response to salbutamol was less in rats treated with L-NAME, compared to those in rats given phenylephrine or the vehicle. These results suggest that endothelium-derived nitric oxide is partially involved in beta 2-adrenoceptor-mediated vasodilatation.

Albuterol↗

PubMed1993

Suppression by ethanol of pressor response caused by the inhibition of nitric oxide synthesis.

The effects of ethanol on mean arterial pressure (MAP) and heart rate (HR) responses to the nitric oxide synthase inhibitor, NG-nitro-L-arginine, and to angiotensin II and noradrenaline were studied in rats. I.V. bolus injections of NG-nitro-L-arginine dose dependently increased MAP in vehicle-pretreated rats, with a maximum increase of 56 +/- 7 mm Hg and an ED50 of 3.8 +/- 0.4 mg/kg, respectively. I.v. infusions of ethanol dose dependently reduced maximum MAP response to NG-nitro-L-arginine, with a Ki of 96 +/- 8 mg/kg per min but did not alter the ED50. Ethanol (48 mg/kg per min) did not modify the MAP response to i.v. bolus injections of angiotensin II (0.02-1.28 micrograms/kg) or noradrenaline (0.25-16 micrograms/kg). However, ethanol attenuated the reflex HR responses of NG-nitro-L-arginine and angiotensin II but not that of noradrenaline. The results demonstrate that ethanol selectively but non-competitively inhibits the MAP response to NG-nitro-L-arginine, suggesting an interaction between ethanol and the L-arginine/nitric oxide pathway.

Angiotensin II↗

PubMed1993

A comparison of the inhibitory effects of sodium nitroprusside, pinacidil and nifedipine on pressor response to NG-nitro-L-arginine.

1. The inhibitory effects of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on mean arterial pressure (MAP) responses to NG-nitro-L-arginine (L-NNA) (NO synthase inhibitor), angiotensin II (AII) and noradrenaline (NA) were compared with those of pinacidil (KATP channel opener) and nifedipine (L-type calcium antagonist) in conscious, unrestrained rats. 2. Intravenous bolus injections of L-NNA (1-64 mg kg-1), AII (0.02-1.28 micrograms kg-1) and NA (0.25-16 micrograms kg-1) dose-dependently increased MAP to similar maxima. Intravenous infusions of SNP (1, 4 and 16 micrograms kg-1 min-1) dose-dependently increased ED20S of L-NNA, AII and NA. However, the maximum response evoked by L-NNA, but not by AII nor NA, was dose-dependently reduced by SNP. Moreover, the inhibitory effect of SNP on the pressor response to L-NNA ceased when the infusion of SNP was terminated. 3. Pinacidil (80 micrograms kg-1 min-1 for 30 min followed by 5 micrograms kg-1 min-1) increased ED50S of L-NNA, AII and NA but did not decrease the maximum responses to any of these agents. 4. Nifedipine (1 mg kg-1 min-1) non-selectively reduced maximum responses to L-NNA, AII and NA to similar levels and increased ED50S of AII and NA but not L-NNA. 5. The results show that SNP causes a selective, non-competitive and reversible inhibition of the pressor response to L-NNA. This inhibition by SNP is unlikely to be related to hypotension, the opening of ATP-sensitive potassium channels or blockade of L-type calcium channels.

Angiotensin II↗

PubMed1993

Halothane inhibits the pressor effect of diphenyleneiodonium.

1. We have recently found that diphenyleneiodonium (DPI), a novel inhibitor of nitric oxide (NO) synthase, causes pressor and tachycardic responses in pentobarbitone- but not halothane-anaesthetized rats. The present study investigated the mechanism by which halothane suppresses the pressor response of DPI. The effects of halothane on the pressor response of DPI were also compared with those of other anaesthetic agents. 2. In conscious rats, i.v. bolus injections of DPI (0.025- 1.6 mg kg-1) caused dose-dependent increases in mean arterial pressure (MAP), with ED90 of 0.07 +/- 0.01 mg kg-1 and maximal rise of MAP (Emax) of 59 +/- 2 mmHg. While ketamine potentiated Emax without altering the ED50 and pentobarbitone increased the ED50 without changing Emax of the pressor response to DPI, chloralose, urethane and ethanol displaced the curve to the right and potentiated Emax. In contrast, halothane (0.5-1.25%) dose-dependently and non-competitively reduced the pressor responses to DPI. 3. Intravenous bolus injection of a single dose of DPI (1.6 mg kg-1) caused immediate and large increases in plasma noradrenaline and adrenaline, as well as MAP in conscious rats. Halothane (1.25%) almost completely inhibited these increases. 4. The results suggest that DPI causes a pressor response in conscious rats by activating the sympathetic nervous system and halothane abolishes this pressor response by inhibiting activities of the sympathetic nervous system. The results also show that influences of anaesthetics must be taken into consideration when evaluating pressor response of vasoactive agents.

Anesthetics↗

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

Influence of intravenous infusion of ethanol on regional blood flow in conscious rats.

The effects of intravenous infusions of ethanol and saline (0.9% NaCl) on mean arterial pressure (MAP), heart rate (HR), total peripheral resistance (TPR), cardiac contractility (dP/dtmax) and systemic haemodynamics were studied in conscious, unrestrained rats by the radioactive microsphere technique. Saline (0.03 and 0.06 mL min-1 kg-1 for 12 min each dose) in the time-control group did not affect MAP, HR, TPR, dP/dtmax or vascular conductances in any organs or beds. While the low dose ethanol (2.4 mg min-1 kg-1) did not alter MAP, HR, TPR, systemic haemodynamics or dP/dtmax, the high dose (4.8 mg min-1 kg-1) slightly reduced MAP and TPR but did not affect HR, cardiac output or dP/dtmax. Both doses of ethanol vasodilated the intestine and spleen, but vasoconstricted the skin. The high dose caused additional vasodilatation in the heart and testes and the low dose also constricted the skeletal muscle bed. Our results show that ethanol, at non-hypotensive or slightly hypotensive doses, has marked vasodilator effects in the heart, intestine, spleen and testes.

Animals↗

PubMed1993

Possible equilibration of portal venous and central venous pressures during circulatory arrest.

The mean circulatory filling pressure technique has been used to assess total body venous tone. It involves measuring central venous pressure (CVP) at 5-8 s following circulatory arrest. This study examines if CVP and portal venous pressure (PVP) equilibrate when circulation is stopped by inflating a balloon implanted in the right atrium. CVP and PVP were measured in the control condition and after intravenous bolus injections of norepinephrine (NE, 1.6 microgram/kg), angiotensin II (ANG II, 1.3 microgram/kg), and isoproterenol (Iso, 0.5 microgram/kg) in conscious and pentobarbital-anesthetized rats. In conscious rats, CVP was similar to PVP after circulatory arrest under conditions of normal, elevated, or reduced vascular tone. In anesthetized rats, CVP was similar to PVP in the control condition and after intravenous bolus injection of NE and Iso but was less than PVP after the administration of ANG II. Therefore, mean circulatory filling pressure may not fully reflect total body venous tone in anesthetized, surgically stressed rats.

Angiotensin II↗

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↗

PubMed1993

Vascular pharmacodynamics of NG-nitro-L-arginine methyl ester in vitro and in vivo.

The inhibitory effects of NG-nitro-L-arginine methyl ester (L-NAME) on endothelium-dependent vasodilatation were studied in conscious rats and isolated rat aortic rings. In phenylephrine (PE, ED90)-preconstricted aortae, L-NAME caused prolonged and complete inhibition of acetylcholine (ACh)-induced relaxation with IC50 of 4 x 10(-7) M and Hill coefficient (n) of 1. The inhibition was abolished by L-arginine (L-Arg), independently of whether it was applied 10 min earlier or 4 hr later than L-NAME. Intravenous bolus injection of L-NAME caused prolonged increases in mean arterial pressure (MAP), with Emax of 50 +/- 7 mm Hg, ED50 of 5 +/- 1 x 10(-6) mol/kg and n of 2. Intravenous infusion of L-Arg shifted the dose-MAP curve of L-NAME to the right without changing Emax or n. A modified Schild plot (n = 2) for the action of L-NAME gave a slope not different from unity, suggesting that L-Arg inhibits competitively the MAP response of L-NAME. Intravenous infusion of ACh decreased MAP in rats treated with L-NAME (4.8 x 10(-5) mol/kg) or PE. Compared to PE-treated rats, L-NAME inhibited the depressor response to ACh by 50%. Thus, a dose of L-NAME 10 times its ED50 in raising MAP only partially blocked the depressor responses to ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1993

In vitro and ex vivo inhibitory effects of L- and D-enantiomers of NG-nitro-arginine on endothelium-dependent relaxation of rat aorta.

The in vitro and ex vivo inhibitory effects of NG-nitro-L-arginine (L-NNA) and NG-nitro-D-arginine (D-NNA) on endothelium-dependent relaxations were studied in rat aortic rings. L-NNA (3 x 10(-7) to 3 x 10(-5) M) but not D-NNA (3 x 10(-6) to 3 x 10(-4) M) induced contraction of resting aortic rings and potentiated phenylephrine-induced contraction in a concentration-dependent manner. In phenylephrine-preconstricted aortic rings, L-NNA (3 x 10(-7) to 3 x 10(-5) M) and D-NNA (3 x 10(-6) to 3 x 10(-4) M) concentration-dependently inhibited the relaxation response to acetylcholine (ACh) with similar efficacies and IC50 values of 10(-6) and 3.9 x 10(-5) M, respectively. In addition, both L-NNA (3 x 10(-5) M) and D-NNA (3 x 10(-4) M) almost totally inhibited the relaxation of preconstricted rings by the calcium ionophore A 23187. The inhibitory effects of L- and D-NNA remained for at least 4 hr after the preparations were washed out. Neither the inhibitory effects of L- and D-NNA on ACh-induced relaxation nor the ACh-induced relaxation itself were affected by pretreatment with indomethacin. However, pretreatment (10 min) or post-treatment (1 hr later) with L-Arg (10(-3) M) completely prevented or markedly reversed the inhibitory effects of L- and D-NNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

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↗