Vascular symptoms in patients with primary Raynaud's phenomenon are not exacerbated by propranolol or labetalol.

Acrocyanosis, Raynaud's phenomenon and intermittent claudication have all been reported either to be caused or exacerbated by }3-adrenergic receptor blockage (Zacharias, Cowen, Prestt, Vickers & Wale, 1972; Marshall, Roberts & Barritt, 1976). The aetiology of primary Raynaud's phenomenon remains controversial (McGrath & Penny, 1974) but the disorder is characterized during acute attacks by a diminution in hand blood flow as determined by digital cutaneous temperatures (Peacock, 1960) or by venous occlusion plethysmography (McGrath, Peek & Penny, 1978). Symptoms generally occur on exposure to cold or to emotional stress (McGrath& Penny, 1974). Propranolol, in the presence of noradrenaline infusions, has been shown to decrease forearm arterial blood flow determined by intra-arterial pressure recordings (Brick, Glover, Hutchison & Roddie, 1966) and forearm blood flow determined by plethysmography (Johnsson, 1967) in normal volunteers. These changes appear similar to those occurring in primary Raynaud's phenomenon. It has been postulated on the basis of animal studies that the underlying vasospastic mechanism in 03-adrenoceptor blocker induced Raynaud's phenomenon is that of the unopposed aadrenergic effect of released noradrenaline on small vessels and capillaries. This may be associated with a decrease in cardiac output and poor peripheral perfusion (Imms, Neame & Powis, 1977; Lundvall & Jarhult, 1976). Propranolol without a noradrenaline infusion appears to have no effect on forearm blood flow (Brick et al., 1966). P-adrenoceptor antagonists now form a most important group of drugs used in the management of hypertension but side effects may limit their use. It seems unlikely that a fall in cardiac output alone could account for the symptoms of vascular insufficiency since a number of other antihypertensives e.g. methyl dopa (Lund-Johansen, 1976) also decrease cardiac output and have not been reported to have these side effects. The possibility that the symptoms are caused by peripheral arteriolar spasm perhaps in association with a decreased cardiac output is more attractive. The introduction of labetalol which has both aand /3adrenoceptor blocking properties (Farmer, Kennedy, Levy & Marshall, 1972) provides an opportunity to test the hypothesis that the a-adrenoceptor blockade induced by labetalol should afford some measure of protection from symptoms. Fourteen patients (nine female, five male) attending the hypertension clinic at the Radcliffe Infirmary volunteered for the study. All had previously complained of pain and whiteness of the fingers on exposure to cold followed by hyperaemia as the hands were rewarmed. Some had previously taken ,B-adrenoceptor blockers and two felt subjectively that they had been worse with ,B-adrenoceptor blockade. All had been symptomatic without any drug therapy. All were mildly hypertensive (Table 1). None had cardiac or renal disease or haemorrhages or exudates on fundal examination. Ages ranged between 38 and 72 years. Four were smokers and the others had given up smoking more than 12 months previously. Chest Xrays of these patients were normal. All gave written informed consent for the study. The trial was run during January to May, 1978. The drugs used were propranolol 80 mg and labetalol 300 mg administered orally twice daily in a randomized double-blind crossover design. Active drugs were taken for 4 weeks with a 2-week placebo run-in period beforehand and a 4-week placebo washout period between active drugs. No other drugs were taken during the trial except aspirin by one patient for osteoarthritis and cyclopenthiazide with potassium chloride by two patients for cyclical oedema. Patients were seen at the start of the trial when they filled in a detailed symptoms questionnaire and underwent a full physical examination. They were seen thereafter at two-weekly periods when the following measurements were made: