Does inadequate oxygen delivery trigger pressor response to muscle hypoperfusion during exercise?

In dogs running on a treadmill at 2 or 4 mph or 4 mph plus 10% incline, graded reductions in hindlimb perfusion reflexly elicited pressor responses. To test the idea that systemic arterial pressure (SAP) is raised by accumulation in muscle of a nerve-activating "pressor substance" release when O2 delivery becomes inadequate, arterial O2 content (CaO2) was reduced 29.1% by carbon monoxide (CO) inhalation before repeating exercise at 2 mph. We reasoned that the pressor substance, or related substances, should appear in femoral venous blood and be correlated to SAP. K+ behaved inappropriately as a signal to raise SAP, i.e., when flow was reduced, SAP rose markedly with little or no change in K+. SAP was well correlated to pH and lactate over the three work loads. Compared with the same work load with normal CaO2, CO shifted the relation between SAP and terminal aortic flow rightward 0.30 l/min (34.5%) and the relation between SAP and PO2 leftward 7.7 mmHg. CO did not affect the relation of SAP to terminal aortic O2 delivery, hindlimb O2 uptake index, pH, or lactate. Thus pressor responses are apparently generated when O2 delivery falls below some critical level causing accumulation of a pressor substance the release of which is linked to a metabolic event that precipitates lactate accumulation.