Enhanced responses to ganglion blockade do not reflect sympathetic nervous system contribution to angiotensin II-induced hypertension

OBJECTIVE: We examined whether a specific increase in sympathetic nervous system (SNS) activity accounts for the enhanced depressor response to ganglion blockade in angiotensin II (AngII)-induced hypertension in rabbits or whether it reflects a general increased sensitivity of arterial pressure to vasodilatation. METHODS: Rabbits were renal denervated or sham-operated and 2 weeks later AngII (50 ng/kg per min) infusion commenced. Mean arterial pressure (MAP) responses to ganglion blockade (pentolinium) and vasodilators nitroprusside and adenosine were measured 2-4 weeks later. RESULTS: Basal MAP was 74 +/- 2 mmHg and maximum hypotensive responses to pentolinium, nitroprusside and adenosine were -17 +/- 2, -17 +/- 1 and -21 +/- 2 mmHg. AngII increased MAP similarly in intact and renal denervated rabbits (+25 +/- 4 mmHg and +31 +/- 4 mmHg, respectively). In intact rabbits, depressor responses to pentolinium were augmented by 75 during AngII infusion but responses to vasodilators also increased by 73-106 suggesting general augmentation of vascular reactivity rather than a specific increase in SNS neural activity. Consistent with this notion, total noradrenaline spillover was similar in normal and AngII-treated rabbits. In renal denervated rabbits, AngII enhanced depressor responses to vasodilators but not pentolinium, suggesting that sympathetic activity may be reduced by AngII hypertension when renal nerves are absent. In anaesthetized rabbits, methoxamine-induced decreases in hindlimb vascular conductance were greater in hypertensive than normotensive rabbits suggesting the presence of vascular hypertrophy of sufficient magnitude to explain increased responses to ganglion blockade and vasodilators. CONCLUSION: Enhanced depressor responses to ganglion blockade in AngII hypertension do not reflect augmented SNS activity, but rather, augmented sympathetic vasoconstriction mediated by a vascular amplifier effect.