Wing Lm

EFFECTS OF P-CHLOROPHENYLALANINE ON BLOOD PRESSURE AND HEART RATE IN NORMAL RABBITS AND RABBITS WITH NEUROGENIC HYPERTENSION

SUMMARY 1. Intraperitoneal administration of p‐chlorophenylalanine (pCPA: 100–400 mg/kg per day) reduced central serotonin concentrations to 20–50% of control in the rabbit.

Diltiazem and atenolol in essential hypertension : additivity of effects on blood pressure and cardiac conduction with combination therapy

In 15 patients with mild to moderate essential hypertension, the effects of diltiazem (120 mg twice daily) were compared with those of atenolol (50 mg once daily), the two drugs in combination, and placebo in a randomized double-blind cross-over study with treatment phases of 4 weeks duration. Blood pressure was reduced in the active treatment phases (supine blood pressure: diltiazem, 172/92 mmHg; atenolol, 172/92 mmHg; diltiazem plus atenolol, 164/88 mmHg; pooled estimate of s.e.m. by analysis of variance = 3/1) compared with placebo (180/101 mmHg). Factorial analysis confirmed fully additive antihypertensive effects of the drugs in combination. The time interval from the beginning of the P wave to the beginning of the QRS complex (P-R interval) was longer during combination therapy (0.184s) compared with either diltiazem (0.175s) or atenolol (0.174s) alone, or placebo (0.164s); s.e.m. by analysis of variance = 0.003. No clinically significant conduction disturbances occurred. Plasma atrial natriuretic peptide was elevated by atenolol but not diltiazem. Thus, in subjects with uncomplicated essential hypertension, diltiazem and atenolol had equal antihypertensive efficacy when used alone, and fully additive effects in combination, on both blood pressure and cardiac conduction.

Effect of Ketanserin On Blood-Pressure and Biochemical Parameters in Patients with Essential-Hypertension

Seventeen subjects with essential hypertension (14 men, 3 women, 40-69 years of age), 13 of whom continued their previous antihypertensive therapy, completed a double-blind crossover trial of ketanserin 40 mg twice daily versus placebo tablets twice daily. Each treatment phase was 6 weeks in duration. For the group as a whole, blood pressure (BP) was reduced in the ketanserin phase compared with the placebo phase: supine mean BP decrease: 4 +/- 1 mm Hg (p less than 0.05); standing mean BP decrease: 7 +/- 1 mm Hg (p less than 0.001). Heart rate (HR) was also significantly decreased in the ketanserin phase (5 +/- 1 beats/min) (p less than 0.001). When individual subgroups were analysed, the reductions in BP and HR were greater in subjects already receiving antihypertensive therapy, diuretics, and/or beta-adrenergic blockers. Changes were observed in 24-h urine sodium and potassium excretion: Sodium (mmol/day): placebo 137 +/- 17, ketanserin 174 +/- 19 (p less than 0.05); potassium (mmol/day): placebo 74 +/- 8, ketanserin 57 +/- 5. For the group as a whole, there were no significant adverse effects during the ketanserin phase, although two subjects had a dose reduction of ketanserin because of drowsiness and dizziness. Two additional subjects withdrew from the study owing to adverse effects, one in the placebo phase. In conclusion, ketanserin in the dose administered has a modest hypotensive effect, which is best seen in subjects already receiving other antihypertensive agents.

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices.

Intracisternal 6-hydroxydopamine (6-OHDA) and 5,6 dihydroxytryptamine (5,6-DHT) in experimental hypertension

Publisher Summary This chapter describes the intra-cisternal 6-hydroxydopamine (6-OHDA) and 5,6 dihydroxytryptamine (5,6-DHT) in experimental hypertension. Small doses of 6-OHDA or of 5, 6-DHT were injected intra-cisternally into New Zealand white rabbits to produce selective ablation of either catecholaminergic or serotonergic nerves in the brain and spinal cord. 5, 6-DHT given intra-cisternally caused a reduction in endogenous serotonin concentration, most marked in the spinal cord, where the levels fell to approximately 25% of control. There were no significant changes in endogenous catecholamine concentrations. Pretreatment with 5,6-DHT caused a small reduction in mean arterial pressure in normal animals, and completely prevented the hypertension that usually follows sinoaortic denervation. It is found that when given to animals with sustained neurogenic hypertension produced by section of the buffer nerves, 5,6-DHT caused a significant fall in arterial pressure, though the pressure remained above initial normotensive control levels. 5,6-DHT given intracisternally did not in any way modify the development of renal hypertension produced by bilateral wrapping of the kidneys with cellophane.

INTRACISTERNAL 6-HYDROXYDOPAMINE (6-OHDA) AND 5,6 DIHYDROXYTRYPTAMINE (5,6-DHT) IN EXPERIMENTAL HYPERTENSION

Publisher Summary This chapter describes the intra-cisternal 6-hydroxydopamine (6-OHDA) and 5,6 dihydroxytryptamine (5,6-DHT) in experimental hypertension. Small doses of 6-OHDA or of 5, 6-DHT were injected intra-cisternally into New Zealand white rabbits to produce selective ablation of either catecholaminergic or serotonergic nerves in the brain and spinal cord. 5, 6-DHT given intra-cisternally caused a reduction in endogenous serotonin concentration, most marked in the spinal cord, where the levels fell to approximately 25% of control. There were no significant changes in endogenous catecholamine concentrations. Pretreatment with 5,6-DHT caused a small reduction in mean arterial pressure in normal animals, and completely prevented the hypertension that usually follows sinoaortic denervation. It is found that when given to animals with sustained neurogenic hypertension produced by section of the buffer nerves, 5,6-DHT caused a significant fall in arterial pressure, though the pressure remained above initial normotensive control levels. 5,6-DHT given intracisternally did not in any way modify the development of renal hypertension produced by bilateral wrapping of the kidneys with cellophane.

Felodipine Compared to Prazosin as Additional Therapy to a Beta-Blocking Drug

Felodipine was compared with prazosin in patients with essential hypertension whose blood pressure was not controlled by a beta-blocking drug. One hundred patients with a supine diastolic blood pressure greater than or equal to mm Hg after 4 weeks or more on a beta-blocking drug and placebo were randomly assigned to felodipine or prazosin tablets. The drugs were titrated at 2-week intervals if diastolic BP was greater than or equal to 90 mm Hg. Titration steps of felodipine were 5, 10, 20 mg b.i.d. and of prazosin were 1, 2, 4 mg b.i.d. The fall in blood pressure with felodipine 32/21 mm Hg was greater than the fall with prazosin 16/12 mm Hg (p less than 0.001); 36 patients achieved a diastolic blood pressure of less than 90 mm Hg with felodipine, which was a significantly greater number than the 20 patients who obtained such a level with prazosin (p less than 0.01). Both drugs were well tolerated, but more patients complained of vascular type side effects (flushing, peripheral edema) with felodipine than with prazosin. There was significant weight gain with prazosin but not with felodipine. Felodipine was shown to be a well-tolerated, effective antihypertensive agent when used with a beta-blocking drug and to be suitable for people with hypertension who fail to be controlled with a beta-blocking drug.