Figure 1.

Schematic representation of the hypothesis that chronic hypoxia sensed by carotid body and kidney is essential for physiological adaptation and when over-activated can contribute to cardiovascular disease due to positive cross-organ interactive feedback mechanisms. We propose a temporal sequence to the reflex responses elicited between the two organs. One potential way of how the transition from one state to the other would occur includes the inability of the kidney to overcome tissue hypoxia during pathological conditions related to hypoperfusion and/or increased metabolic rate (e.g., vasoconstriction, mitochondrial dysfunction, hyperfiltration). Signals cascading from the hypoxic kidney activate the carotid body that acts cooperatively to ensure sustained (and in the end aberrant) long term sympathoexcitation. Furthermore, the renin angiotensin system is activated in both organs in response to low blood flow/hypoxia. This chronic low blood flow/hypoxia together with the activation of the renin angiotensin system forms a non-functional positive feedback loop that leads to tissue damage. Increasing the renin angiotensin system will lead to activation of different pathways to ensure proper oxygen delivery, including hypoxia inducible factor and erythropoiesis, that may also contribute to the dysfunctional sympathetic activation in hypertension.