Hypertension has become a serious and expensive public health problem with more than 1.3 billion people affected worldwide. In ~90% of cases the cause of high blood pressure is unknown (primary or essential hypertension), and a significant proportion (~7-14%) of hypertensive patients remain drug resistance or intolerant to medication. Thus, better understanding of the control of blood pressure in physiological and pathological circumstances is necessary to understand basic mechanisms and unveil new therapeutic targets. Unequivocal evidence supports chronic activation of the sympathetic nervous system as a characteristic of hypertension. We and others have found evidence suggesting that hyperactivity in afferent nerves from the carotid bodies and renal dysfunction are mutually involved in the initiation, maintenance and progression of hypertension. We hypothesize that the kidney and carotid body cooperate synergistically to optimize organ blood flow and tissue oxygen homeostasis. Under pathological conditions of severe or prolonged (renal) tissue hypoxia, these sensors become over activated resulting in hypertension. We aim to map the time course of events during the genesis of hypertension and how it relates with long-term renal dysfunction and sympathetic hyperactivity with or without carotid body imput. In order to do this we use radio-telemetry for long-term recording of blood pressure, tissue partial pressure of oxygen, and sympathetic nerve activity in awake and freely moving rats with inducible renovascular hypertension (2-kidney-1-clip) and compare these with relevant sham-operated controls. A solid state pressure sensor is placed in the abdominal aorta to measure blood pressure in male Wistar Rats with or without 2-kidney-1-clip to generate renovascular hypertension, and with or without sectioning the carotid sinus nerve. In two sub-groups of animals, either partial pressure of oxygen from the renal cortex or renal nerve activity is measured continuously. After 6 weeks of follow-up, renal hemodynamics and oxygen metabolism is evaluated under thiobutabarbital anaesthesia. This animal model of physiology and pathophysiology has been recently established in Exeter; with successful removal of the carotid body input resulting in 9±0.01% mean arterial pressure reduction. If we understand more about long-term regulation and the sequence of events leading to hypoxia, hypoperfusion and coincident elevation of sympathetic nervous system activity, we might be able to intervene earlier, more targeted, and change the progression of renal and cardiovascular disease.