Interactions between central and peripheral respiration's control cells in humans with high blood pressure.

This is a non-therapeutic mechanistic physiological study. All the following measurements and tests described will be conducted by a trained human physiologist staff member. At an initial visit to the laboratory, written informed consent will be obtained from participants who will then undergo screening and familiarization. Anthropometric (height, weight, hip-to-waist ratio), demographic, clinical history information will be obtained, and health questionnaires and 7-day physical activity recall data will be collected. Participants will then attend a single experimental session lasting ~3 hours, including set-up time. Experimental sessions will be scheduled ~2-7 days after the initial familiarisation / screening visit, as appropriate. However, premenopausal women will be studied during the first five days of their menstrual cycle (early follicular phase) or during the placebo/no-hormone phase of oral contraceptive use, as appropriate. At the experimental session, participants will be asked to lie in a semi-recumbent position on a medical examination couch and to remain in that position throughout the session. Bilateral internal carotid and vertebral artery blood flow will be measured using duplex Doppler ultrasound. This ultrasound examination is similar to scan done for pregnant women, but a large artery is examined. This is a simple and safe procedure and involves a probe being put on the patients’ skin over the region of interest with the help of a ‘water jelly’. Participants will then be instrumented for continuous monitoring of BP, heart rate (HR), respiration, brachial artery blood flow and sympathetic nerve activity. More specifically, brachial BP will be measured with a clinically validated automated sphygmomanometer (Omron), using a cuff wrapped around the upper arm. In addition, beat-to-beat BP will be measured using finger photoplethysmography, using a small lightweight cuff wrapped around the finger. Heart rate will be measured using standard electrocardiogram involving the placement of several sticky patch electrodes on the collarbones and chest (standard 3 lead ECG). For breathing monitoring, participants will wear a mouthpiece/noseclip or oronasal mask (Hans Rudolph) and chest movements will be monitored with a belt placed around the thorax. Sympathetic nerve activity will be measured using the microneurgraphy technique. This involves the insertion of a small, sterile wire (unipolar tungsten microelectrodes, tip measuring 1-5 um) near the fibular head on the outside of the leg, to obtain a multiunit recording of postganglionic muscle sympathetic nerve activity from the peroneal nerve. After a resting baseline of 20 min (last 5 min used for analysis), chemoreflex testing will be undertaken. Chemoreflex testing will involve five tests. Each test lasts 5 min and is separated by 15 min rest period. Each participant will receive all five tests in a randomised order. Each test involve the breathing of a different gas mixture, while the participant wears a mouthpiece/noseclip or oronasal mask. The five tests are: 1) hypercapnic hyperoxia (to evaluate central chemoreflex stimulation with diminished peripheral chemoreflex stimulation, using a gas concentration of: 7% CO2, 50% O2 and 43% N2); 2) isocapnic hypoxia (to evaluate peripheral chemoreflex stimulation, using a gas concentration of: 10% O2 and 90% N2); 3) hypercapnic hypoxia (to evaluate combined central and peripheral chemoreflex stimulation, using a gas concentration of: 7% CO2, 10% O2 and 83% N2); 4) isocapnic hyperoxia (to evaluate potential central effects of hyperoxia, using a gas concentration of: 50% O2 and 50% N2); and 5) hypocapnic hyperoxia (to evaluate central chemoreflex tonicity, using a gas concentration of: 50% O2 and 50% N2 which will be conducted with a rebreathing test).