Relative Contribution of Endothelium-Derived Relaxation Factor to Vascular Tone in the Systemic, Pulmonary, and Cerebral Circulations of Piglets

Abstract

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.

Effect of an acute increase in central blood volume on cerebral hemodynamics

“…These findings indicate that it is the cerebral vascular tone that determines CBF responses to cerebral hyperperfusion or hypoperfusion conditions. Therefore, the differential response observed between the cerebral and systemic vasculature in the present study may be explained by the greater autoregulatory (myogenic) and adrenergic receptor vasoconstrictive properties of the cerebral blood vessels compared with systemic blood vessels (46). In the present study, the estimated cerebral perfusion pressure at the MCA was acutely and largely increased during microgravity despite a decrease in MAP ( Figs.…”