We determined the contribution of endothelium-derived relaxation factor
(EDRF) to vascular tone in the systemic, pulmonary, and cerebral circulations
of piglets. Methods: 11 piglets were anesthetized and mechanically
ventilated. Systemic cardiac output was determined by an electromagnetic
flow probe placed on the main pulmonary artery. Cerebral blood flow was
assessed by determining unilateral internal carotid artery blood flow
(ICBF) using a flow probe placed on the common carotid artery after ligation
of the ipsilatcral external carotid circulation. Progressive inhibition of
EDRF was achieved by continuous infusion of the substituted /.-arginine
analog N-nitro-L-arginine (NNLA). Hemodynamic observations were
compared at 0, 0.1, 1.0, 10, 30, and 80 mg/kg cumulative dose of NNLA.
Results: At all NNLA doses ≥ 1 mg/kg, both systemic blood pressure and
systemic vascular resistance were elevated. At all NNLA doses ≥ 10 mg/
kg, systemic cardiac output was reduced. At all NNLA doses ≥ 10 mg/kg,
pulmonary artery pressure and pulmonary vascular resistance were elevated.
Although cerebral vascular resistance was elevated at all NNLA
doses ≥ 10 mg/kg, ICBF was maintained at or near baseline values up to a
dose of 80 mg/kg. At all levels of EDRF inhibition, both the pulmonary
and systemic circulations demonstrated approximately equal magnitudes
of vasoconstriction. In contrast, at 30 and 80 mg/kg cumulative dose of
NNLA, the cerebral circulation was relatively less constricted by NNLA
than was the systemic circulation. Systemic VO(2) was significantly reduced
at 30 mg/kg and 80 mg/kg cumulative NNLA dose, while cerebral VO(2)
was preserved at both NNLA doses. Conclusions: EDRF contributes to
resting vasodilator tone in the systemic, pulmonary, and cerebral circulations
in piglets. Progessive inhibition of EDRF constricts the systemic and
pulmonary circulation equally. Inhibition of EDRF does not impair the
ability of the brain to vary cerebral vascular resistance in order to redistribute
blood flow towards itself during a period of reduced cardiac output.