Dissociation of sympathetic compensation from glyceryl trinitrate tolerance

The hypothesis that changes in sympathetic function play an integral part in the development of tolerance to the vasodepressor effects of organic nitrates was tested. Glyceryl trinitrate (GTN) tolerant rats showed increased norepinephrine turnover but no changes in myocardial norepinephrine levels or in uptake of exogenous norepinephrine. GTN tolerant animals did not have altered sensitivities to sympathomimetics. Marked changes in sympathetic tone did not change the animals' sensitivity to glyceryl trinitrate (GTN) and did not alter the development of tolerance to GTN. No changes in sympathetic compensation to direct administration of a vasoconstrictor to the carotid sinus were observed. It is concluded that changes in sympathetic function play no rule in the development of tolerance to GTN.