The primary aim of the present study was to examine the haemodynamic changes in primary hypertension and secondary hypertension (renal diseases, endocrine diseases, obesity-associated hypertension) with a non-invasive haemodynamic measurement protocol utilizing radial pulse wave analysis and whole-body impedance cardiography in both supine position and during head-up tilt. For comparison, haemodynamics of subjects with chronic fatigue syndrome will also be recorded.

Elevated blood pressure (BP) and related cardiovascular complications are the leading causes of morbidity and mortality in the modern world. In routine clinical practice, the haemodynamic status is commonly assessed by measuring heart rate and blood pressure at rest, which provides only limited information about functional haemodynamic status. In addition, the haemodynamic changes resulting in similar elevations of BP may differ substantially between patients and disorders.

Therefore, we investigated the haemodynamic changes in primary and secondary hypertension and in the control subjects with non-invasive radial pulse wave analysis and whole-body impedance cardiography. The method includes the determination of volume status using bioimpedance spectroscopy, determination of peripheral and central BP, cardiac function, vascular resistance, arterial compliance and indices of pulse wave reflection. Besides the measurements performed in the supine position, passive orthostatic challenge is included in the protocol to assess the upright functional haemodynamic status.

The repeatability and reproducibility of the protocol was first examined with a double-blind, randomized protocol in 35 subjects (methodological study group), and after that the administration of research drugs has been open-label. The effects of single doses of two largely endothelium-dependent agents, inhaled salbutamol and intravenous L-arginine, and one endothelium-independent agent, sublingual nitroglycerin, were investigated. However, challenges with the acute dosing of all medical compounds was terminated at the end of December 2016. Thereafter, the measurement protocol has included supine and upright recordings on the tilt-table, followed by supine measurements during paced breathing (15 breaths per minute for 5 minutes, 6 breaths per minute for 5 minutes) that modulate the autonomic nervous tone.

The study population has consisted of subgroups described below. The study protocol of each subgroup has been approved by the ethics committee of the Pirkanmaa Hospital District (Ethics committee ID's above), and the administration of research drugs has also been approved by the Finnish Agency for Medicines (EudraCT-numbers above).

Inclusion Criteria:

• Independent, community-dwelling adults
• Hypertensive subjects (primary or secondary hypertension)
• Normotensive control subjects
• Subjects with aortic stenosis (subgroup "aortic stenosis")
• Participants of Ironman Triathlon competition

Exclusion Criteria:

• Pregnancy
• Systolic blood pressure <90 mmHg
• Allergies to test compounds

Adult hypertensive and normotensive subjects who were treated in Tampere University Hospital clinics of internal medicine or cardiology, or visited medical doctors as outpatients at occupational health care providers in the Pirkanmaa Hospital District.

Patients with primary aldosteronism from all University clinics (Helsinki, Turku, Kuopio, Oulu) in Finland, who were referred to Tampere University Hospital for adrenal vein sampling.

Patients with acromegalia from all University clinics (Helsinki, Turku, Kuopio, Oulu) in Finland.

Participants of Ironman Triathlon competition.