There are 3 clinical trials
Dopamine (DA) is one of the main catecholamines in mammals. Its major role as a brain neurotransmitter is well known as well as its contribution to the development of pathologies, mainly arterial hypertension. Traditionally, dopamine receptors are divided into two families according to the stimulation or inhibition they may produce at the adenyl cyclase level. Five dopamine receptors have been identified: D1 (D1a) and D5 (D1b) exist in the D1 family. D2s, D2l, D3 and D4 belong to the D2 family. Formerly, less than 1% of patients with hypertension were believed to have primary hyperaldosteronism; however, recent studies have suggested that primary aldosteronism affects 5-13% of patients with hypertension and aldosteronomas are a more common cause of hypertension than previously thought. At least 2% of patients with hypertension may have an aldosteronoma. The investigators' previous clinical observation found two subtypes of aldosterone-producing adenoma (APA), which were defined according to their responses to metoclopramide during salt manipulation. On a high-salt diet (HS), the nonsuppressible subjects, with less dopaminergic inhibition of aldosterone secretion, had less urinary DA excretion and greater blood pressure (BP) elevation [Wu KD et al. 2002]. The investigators' recent study of six patients with an APA found that the expression of the D2 receptor in APA was not universal. The amounts of D2 receptor messenger ribonucleic acid (mRNA) were more variant in either APA or their remnant adrenal glands. Only two cases of APA expressed the D2 receptors with much weaker signals compared with those in their respective remnant adrenals [Wu KD et al. 2001]. The investigators' current work demonstrates that the D2 receptor negatively regulates AII-stimulated aldosterone secretion and aldosterone synthase mRNA expression in NCI-H295R cells. On the other hand, the D4 receptor counteracts with the effect of the D2 receptor. In a future study, the investigators wish to quantify D2 and D4 receptor mRNA and protein expression in APA and their remnant adrenal glands and correlate them to their clinical metoclopramide test results. The investigators also wish to know whether the difference between the D2 and D4 receptor expression reflect the different effects of dopamine inhibition on AII-stimulated aldosterone secretion and aldosterone synthase transcription. Finally, the investigators will explore the role of D2 and D4 receptors on AII-stimulated adrenal cell proliferation.
The investigators' current work demonstrates that the D2 receptor negatively regulates AII-stimulated aldosterone secretion and aldosterone synthase mRNA expression in NCI-H295R cells. --- H295R ---
Project titel: Oral potassium supplementation in healthy men - interactions with the renin-angiotensin-aldosterone system and the sympathetic nervous system Protocol number: KARAASS-1 EudraCT number: 2013-004460-66 Introduction The global burden of hypertension is huge. This project focuses on the role of potassium in human blood pressure regulation. A potassium rich diet lowers blood pressure and some studies have shown an increase in blood pressure during potassium depletion. Thus an inverse correlation between potassium intake and blood pressure exists. In this trial the objective is to test how an oral potassium supplementation, administered in form of the drug Kaleorid®, interacts with the renin-angiotensin-aldosterone system and the sympathetic nervous system. Methods This is a randomized clinical placebo-controlled double-blinded crossover trial. A group of healthy men will be randomized to either 4 weeks treatment with the drug Kaleorid®, 750mg, 3 tablets 3 times daily or to 4 weeks treatment with placebo. On day 26 in the first treatment period the participants meet at the hospital to start a 24-hours ambulatory blood pressure and collect a 48-hours urine sample. The same day a blood sample, an electrocardiogram (ECG) and a fat biopsy from the gluteal region will be done. The fat biopsy is expected to contain resistance vessels, which are to be investigated further in the laboratory. On day 28 in the first treatment period the participants meet at the hospital again and are tested with an intravenous Angiotensin II infusion followed by continuous measurement of blood pressure and the following aldosterone response (using blood samples). Blood pressure will be measured with Finger Plethysmography and vascular tonus will be evaluated with the use of Impedance Cardiography, Finger Plethysmography and Doppler Ultrasound measurements of blood flow before, during and after the Angiotensin II infusion. After this first period of treatment and testing a "washout" period of two weeks is inserted. After "washout", the participants crossover and starts the second treatment period. Feasibility All necessary authorities have approved the trial and all cooperation is established.
Working with an in vitro model of aldosterone secretion in the form of the human adrenocortical cell line H295R, which has been proven to be a model for studying the function of the human adrenal cortex (13;14), we found interactions between extracellular potassium and components of the renin-angiotensin-aldosterone system (RAAS). --- H295R ---
The H295R cell line is a model of the human adrenocortical zona glomerulosa cells, which normally are the site of synthesis and secretion of aldosterone in the human body. --- H295R ---
It was found that stimulation of the H295R cells with high levels of extracellular potassium decreased the amount of Ang II type 1 receptors in the membrane of the cells, measured as a fall in the specific binding of radioactive labelled Ang II to the cells (15). --- H295R ---
Background: The adrenal gland makes the hormone aldosterone. This helps regulate blood pressure. An adrenal gland tumor that makes too much aldosterone can cause high blood pressure and low potassium. The cause of these tumors is unknown, but sometimes they are inherited. Objective: To study the genes that may cause primary aldosteronism in Black individuals. Eligibility: People ages 18-70 who: Are Black, African American, or of Caribbean descent And have difficult to control blood pressure or primary aldosteronism Relatives of people with primary aldosteronism Design: Participants who are relatives of people with primary aldosteronism will have only 1 visit, with medical history and blood tests. Participants with primary aldosteronism or difficult to control blood pressure (suspected to possibly have primary aldosteronism) will be screened with a 1-2 hour visit. If they qualify, they will return for a hospital stay for 7-10 days. Tests may include: Medical history Physical exam Blood tests: Participants will have a small tube (IV catheter) inserted in a vein in the arm. They may drink a glucose-containing liquid or get a salt solution. If medically indicated, they may have invasive blood tests with a separate consent. Urine tests: Some require a high-salt diet for 3 days. Heart tests Scans: Participants lie in a machine that takes pictures of the body. A dye may be injected through a vein. Small hair sample taken from near the scalp. Kidney ultrasound Bone density scan: Participants lie on a table while a camera passes over the body. If the doctors feel it is medically necessary, they will offer participants treatment depending on their results. These treatments may cure the patient of their disease and may include: 1. Having one adrenal gland removed by the Endocrine surgeon under anesthesia. Patients will have follow-up visits 2-4 weeks after surgery. 2. Taking drugs to block the effects of aldosterone Participants may return about 1 year later to repeat testing.
Human adrenal cell lines (H295R and others, as appropriate) will be used to study the mutations effect on aldosterone production. --- H295R ---
Description: define the causes of PA in AA and develop new therapeutic strategies to inhibit the inappropriate aldosterone production.Measure: To define the germline and/or somatic genetic events causing Primary Aldosteronism (PA) in Blacks. Time: baseline, end of study
Description: define the causes of PA in AA and develop new therapeutic strategies to inhibit the inappropriate aldosterone production.Measure: To define the effects of mutations in Black subjects on adrenocortical tumor formation, function and aldosterone production. Time: Continuous
Description: define the causes of PA in AA and develop new therapeutic strategies to inhibit the inappropriate aldosterone production.Measure: To investigate co-secretion of other steroids in PA. Time: baseline, end of study