1. The effects of graded intravenous infusions of sodium nitroprusside on resting blood pressure and heart rate and on the reflex changes in these variables evoked by a standardized Valsalva manoeuvre were studied in six normal subjects. The effects of nitroprusside on the above variables were also studied after pre-treatment with captopril, to allow assessment of the role of angiotensin II.

2. Nitroprusside given in doses ranging from 7.5 to 150 μg/min elicited dose-related decreases in resting blood pressure and rise in heart rate and in plasma renin activity (PRA). After pretreatment with captopril, nitroprusside could not be given at doses above 60 μg/min without producing an unacceptable fall in blood pressure. The rise in heart rate in response to a given dose of nitroprusside was little altered after captopril.

3. Blood pressure and heart rate were studied during the last 10 s of the Valsalva manoeuvre. Before captopril the normal response (maintenance of blood pressure with tachycardia) was not altered by any dose of nitroprusside. Captopril alone also had no effect on the response but, with captopril plus high dose nitroprusside, mean arterial pressure during the manoeuvre decreased significantly, indicating impairment of reflex constrictor response.

4. These findings support the proposition that the angiotensin II response normally limits the fall in blood pressure during vasodilator therapy. We conclude that the greater fall in blood pressure and the impaired constrictor response to the Valsalva manoeuvre during nitroprusside infusion at moderate doses, in the presence of captopril, is due to the effect of the latter on the renin—angiotensin system.

5. A practical consequence of the present findings is that combined use of captopril and arterial vasodilators requires reduction in the dose of the latter drug. Awareness of this interaction may avert hypotension and could also allow nitroprusside infusion for longer periods without toxicity.

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