Flow modulation of pressure-sensitive tone in rat pial arterioles: role of the endothelium.

BACKGROUND: Cerebral arteriolar tone is modulated in response to changes in transmural pressure and luminal flow. The effect of flow on the relation between pressure and diameter has not been fully evaluated in these vessels. This study was conducted to investigate this interaction and to determine the role of the endothelium in mediating it. METHODS: Rat pial arterioles from the territory of the posterior cerebral artery were mounted in a perfusion myograph. In some arterioles, the endothelium was removed by air perfusion. Diameters were recorded at pressures from 20 to 200 mmHg in the presence and absence of flow (10 microl/min). The response to flow (0-30 microl/min) was recorded at 60 and 120 mmHg. RESULTS: In the absence of flow, endothelium-intact arterioles demonstrated tone at distending pressures between 40 and 140 mmHg. In the presence of flow, tone did not develop until pressure exceeded 100 mmHg, and the vessels remained active at pressures up to 200 mmHg. Endothelium-denuded arterioles developed tone at the same pressure when perfused as when unperfused, but perfused vessels were able to maintain active tone at higher pressures. At 60 mmHg, flow caused dilation if the endothelium was intact and constriction if it had been removed. At 120 mmHg, flow caused constriction. Endothelium-dependent flow-relaxation was inhibited by N(G)-nitro-L-arginine methyl ester (10(-5) M) and abolished by indomethacin (10(-5) M). CONCLUSION: Flow inhibits the development of pial arteriolar tone at low intraluminal pressures through endothelium-dependent mechanisms. Conversely, perfusion extends the upper limit of the myogenically regulated pressure range through endothelium-independent activation of arteriolar smooth muscle contraction.

Effect of tidal volume and PEEP in ethchlorvynol-induced asymmetric lung injury.

We examined the effects of positive end-expiratory pressure (PEEP) and tidal volume on the distribution of ventilation and perfusion in a canine model of asymmetric lung injury. Unilateral right lung edema was established in 10 animals by use of a selective infusion of ethchlorvynol. Five animals were tested in the supine position (horizontal asymmetry) and five in the right decubitus position (vertical asymmetry). Raising PEEP from 5 to 12 cmH2O improved oxygenation despite a redistribution of blood flow toward the damage lung and a consistent decrease in total respiratory system compliance. This improvement paralleled a redistribution of tidal ventilation to the injured lung. This was effected primarily by a fall in the compliance of the noninjured lung due to hyperinflation. The effects of higher tidal volume were additive to those of PEEP. We propose that the major effect of PEEP in inhomogeneous lung injury is to restore tidal ventilation to a population of alveoli recruitable only at high airway pressures.

The cardiopulmonary and renal hemodynamic effects of norepinephrine in canine pulmonary embolism.

Autologous blood clot was injected into six dogs to produce a graduated decrease in cardiac output (CO). The effects of an infusion of norepinephrine, titrated to specific end points, were recorded before embolization and at two levels of pulmonary hypertension. Simultaneous measurements of systemic and renal hemodynamics were made. Sequential blood clot injection increased (p less than .01) pulmonary vascular resistance (PVR) from 1.3 to 13 to 33 mm Hg.L-1.min and reduced CO 45 percent and 75 percent (p less than .01). Norepinephrine increased both stroke volume and CO (p less than .01) in each condition and did not increase PVR. Since the biventricular filling pressures remained constant or fell slightly with norepinephrine, the increase in CO is best explained by an improvement in pump performance. There was no deterioration in renal blood flow or creatinine clearance with norepinephrine. The data suggested that in this model of right ventricular dysfunction, norepinephrine consistently improved myocardial performance without provoking further vasoconstriction in either the pulmonary or renal circulations.