Converting enzyme inhibition attenuates the noradrenaline response to the Valsalva maneuvre.

ABSTRACT

HYPOTHESIS: Reduction of plasma angiotensin II inhibits release of noradrenaline in response to a sympathetic nervous system stimulus. OBJECTIVE: To compare heart rate and plasma catecholamine responses to the Valsalva maneuvre before and after inhibition of angiotensin converting enzyme. DESIGN: Four weeks of placebo (all patients). If sitting diastolic blood pressure was found to be between 100 and 115 mmHg, then double-blind randomization to receive 2.5, 5, 10 or 20 mg of quinapril bid for a further four weeks. SETTING: Ambulatory hypertension clinic with admission to clinical investigation unit overnight for interventions. PATIENTS Uncomplicated essential hypertensives of English-Irish ancestry. Twenty-five eligible patients completed the study, while three additional patients withdrew early. INTERVENTIONS: Blood pressure and heart rate were monitored weekly during placebo, and biweekly during active treatment. Patients were rehearsed in performance of the Valsalva maneuvre. At the end of the placebo and active therapy phases, each patient performed standard Valsalva maneuvres immediately before and 2 h after the morning dose of placebo or active drug. Heart rate was recorded continuously throughout the maneuvre, while blood was sampled for catecholamine determinations prior to the start of straining and again approximately 10 s following the end of straining. MAIN RESULTS: Heart rate responses to the Valsalva maneuvre were not affected by acute administration of quinapril, but a slight attenuation of the tachycardic response was seen after four weeks of therapy (P less than 0.05). An increase in plasma noradrenaline concentration associated with the straining phase of the Valsalva maneuvre was markedly attenuated after both acute and chronic quinapril therapy (P less than 0.01). CONCLUSION: By blocking biosynthesis of angiotensin II, converting enzyme inhibition may attenuate baroreceptor-stimulated release of noradrenaline.