Hypertension remains the main preventable cause of cardiovascular disease (CVD) and all-cause mortality, both in Europe and globally. Resistant hypertension, a severe phenotype of hypertension, is defined as a blood pressure (BP) that remains above the management goal despite using three different antihypertensive agents of different classes at the maximum or maximum tolerated dose, or controlled BP on four or more antihypertensive medications. Hypertension remains a poorly controlled risk factor on a global scale and the prevalence of resistant hypertension is also growing - it is now estimated to be around 10-20%.

At the moment, there is robust evidence establishing the antihypertensive effects of exercise. The acute reduction of BP after a single bout of exercise is known as post-exercise hypotension.

In recent years, the number of investigations into the benefits of isometric exercise in the treatment of hypertension has increased, due to its ease of access and potential for use. In a recently published meta-analysis, the authors pointed to isometric exercise as the most effective type of exercise in reducing systolic and diastolic BP.

Given the scarceness of data regarding the safety and efficacy of isometric exercise in individuals with resistant hypertension and since the acute response to exercise may help to identify people who respond to exercise as antihypertensive therapy, the objective of this study is to analyse the acute effect on BP levels of two different isometric exercises - isometric handgrip (IHG) and isometric wall squat (IWS), regarding safety and efficacy, in people with resistant hypertension.

The aim is to analyse if isometric exercises are safe in this population, through the assessment of BP during the execution of the exercises. Besides that, the comparison of IHG and IWS with the control session and between one and another, will help to understand which form of isometric exercise is most effective and has the longest lasting impact on reducing BP.

Each participant must complete an acclimatization session, in which the procedures will be explained, data will be collected and the intensity of IHG and IWS will be assessed. Subsequently, each participant must complete three randomly assigned experimental sessions: a non-exercise control session and two exercise sessions, in which they will follow the protocols currently used in the literature (IHG at 30% of Maximum Voluntary Contraction and IWS at 95% of peak Heart Rate).

Inclusion Criteria:

• Adults aged 40 to 75 years old, previously diagnosed with resistant hypertension, and on stable medication for at least 6 months.

Exclusion Criteria:

• People with secondary hypertension, heart failure, peripheral artery disease, atrial fibrillation, chronic obstructive pulmonary disease or renal failure; people with a cerebro-cardiovascular event in the previous 3 months; people with changes in pharmacological therapy in the previous 6 months; trained people (with regular participation (≥ 2x/week) in exercise training programs in the previous 3 months); people who have any contraindication to exercise; people with neurological and/ or orthopaedic conditions that will interfere with their participation in exercise, such as Parkinson's disease or knee osteoarthritis. Participants with low score (<6) on the MMAS-8 will also be excluded.

Individual participant data that underlie the results of this article, after deidentification.

IPD will be available after publication of the main results and up to five years.

Individual participant data will be available for researchers who provide a methodologically sound proposal (e.g. individual participant meta-analysis).