A comparison of some cardiovascular properties of propranolol, MJ 1999 and quinidine in relation to their effects in hypertensive animals

382

127

Summary Both MJ 1999 and AH 3474 protected guinea‐pigs anaesthetized with urethane against ouabain‐induced ventricular fibrillation. MJ 1999 had 1/90, and AH 3474 1/30, of the activity of procaine in reducing the height of the action potential of frog sciatic nerve. MJ 1999 and AH 3474 reduced the rate of rise of intracellularly recorded action potentials at concentrations in excess of 160 × 10−6m (50 mg/l.). It was concluded that direct depression of depolarization could have contributed little to the protection against ouabain‐induced fibrillation. MJ 1999, but not AH 3474, greatly prolonged the duration of the action potential in acute experiments on isolated atrial and ventricular muscle, and prolonged the Q‐Tc interval of the electrocardiogram in anaesthetized guinea‐pigs. It is suggested that this effect contributes to anti‐arrhythmic activity. At concentrations up to 80 × 10−6m AH 3474 had positive chronotropic and inotropic effects on isolated rabbit atrial muscle, but at higher concentrations these were superseded by negative effects. MJ 1999 was depressant at all concentrations studied, the threshold concentrations being 19 × 10−6m for chronotropic, and 162 × 10−6m for inotropic effects.

Section: Inotropic Actionmentioning

confidence: 60%

Section: Resultsmentioning

confidence: 99%

A third class of anti‐arrhythmic action. Effects on atrial and ventricular intracellular potentials, and other pharmacological actions on cardiac muscle, of MJ 1999 and AH 3474

Singh

Williams

1970

382

127

“…The dosage of atropine was 0.35 ymol kg-1 (Yokotani & Osumi, 1986), the dosage of phentolamine 3.5 pmol kg-1 (Ruwart et al, 1980), and the dosage of propranolol 1.5pmolkg-1 (Farmer & Levy, 1968). The solutions of pentagastrin and [14C]-aniline used for intravenous infusion were also prepared with saline.…”

Section: Substances and Solutionsmentioning

confidence: 99%

Intragastric capsaicin enhances rat gastric acid elimination and mucosal blood flow by afferent nerve stimulation

Lippe

Pabst

Holzer

1989

100

1 This study investigated the effects of intragastric capsaicin on acid output, clearance of aniline, potential difference, and morphology of the mucosa in the rat stomach. The experiments were carried out on rats anaesthetized with urethane in which the stomachs were continuously perfused with saline.2 When the stomach was perfused with normal saline (pH -6), intragastric capsaicin (32-640juM) had no effect on the output of titratable acid. In contrast, when acid output was stimulated by pentagastrin or when the stomach was perfused with acid saline (pH 3), capsaicin reduced acid output. Acid loss which occurred during perfusion with saline of pH 2 was not significantly increased by capsaicin. This suggests that capsaicin does not enhance acid back-diffusion but facilitates acid elimination by other means.3 The gastric clearance of ["4C]-aniline, which is an indirect index of gastric mucosal blood flow, was estimated while the stomach was perfused with saline of pH 3. The clearance of aniline rose by 50-60% following intragastric administration of capsaicin (160 gM) whereas the mean arterial blood pressure was increased by about 2.5 mmHg only. Combined pretreatment of the rats with atropine, phentolamine, and propranolol did not alter the effect of capsaicin on the gastric clearance of aniline. 4 The gastric potential difference was not altered by capsaicin (160juM) administered together with saline of pH 3. This and the finding that there were no signs of mucosal damage by light and scanning electron microscopy indicate that intragastric capsaicin does not irritate the gastric mucosa.5 The effects of intragastric capsaicin on gastric acid output and aniline clearance and on blood pressure were absent in rats in which capsaicin-sensitive afferent neurones had been ablated by neonatal treatment with a neurotoxic dose of capasicin, which indicates that they result from stimulation of afferent nerve endings in the stomach. It is concluded that facilitation of acid elimination and mucosal blood flow may contribute to the previously reported protective action of capsaicin on the gastric mucosa.

“…In the propranolol-treated group, in contrast, there was a small but significant fall in mean diastolic pressure after 6 weeks. Farmer & Levy (1968) (Raine & Pickering, 1977). In matched control (untreated) patients, Q-T shortened from 0.38 to 0.27 during exercise (and QT, from 0.42 to 0.40) but in patients on long-term fl-blockade Q-T shortened from 0.40 to only 0.33 on exercise (and QT, lengthened from 0.41 to 0.42).…”

Section: Discussionmentioning

confidence: 99%

Adaptational Responses to Prolonged Β‐adrenoceptor Blockade in Adult Rabbits

Raine

Williams

1980

A method for measuring propranolol concentrations in plasma has been modified to permit estimations to be made on small volumes. The method has been used to correlate blockade of heart rate increases in response to intravenous isoprenaline, in both young and adult rabbits, with plasma concentrations of propranolol after subcutaneous injections of 2 or 4 mg/kg. It has been found that the relation between β‐adrenoceptor blockade and plasma concentrations is the same in rabbits as that determined by previous workers in man. Adult Dutch dwarf rabbits were treated for 9 weeks twice daily subcutaneously with 2 mg/kg propranolol, or 10 mg/kg practolol, or with saline. The treatment caused no change in heart weight in relation to body weight or in the water content of the hearts, in contrast to effects previously observed in young rabbits. As in the young rabbits, treatment did cause a prolongation of action potential duration, as measured with intracellular electrodes in hearts of animals killed 24 h after the last dose of drug. In another series of experiments, with a similar regime of treatment for 6 weeks, a significant reduction of diastolic blood pressure was observed in the propranolol group. During the course of treatment and at the end, there was no change in the heart‐rate increases observed in response to intravenous isoprenaline administered not less than 15 h after the previous dose of β‐blockers. Thus no functional alteration in sensitivity to β‐adrenoceptor stimulation was apparent.