Cardiovascular System

The cardiovascular system consists of the heart, blood and blood vessels. These organs form the 3 major closed circulation systems in the body, i.e., the pulmonary, coronary and systemic circulations. Cardiovascular disease includes heart disease, vascular diseases of the brain and kidney, and peripheral arterial diseases. Cardiovascular disease is the leading cause of death globally. Studies on cardiovascular regulation are important to provide a better understanding of this group of diseases and to help improve the corresponding treatment.

Regulation of hemodynamics occurs through local autoregulation, neural control and cardiovascular hormones. Here, we focus on hormone regulation.

Natriuretic peptides consist of three homologous members: Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). They bind and activate natriuretic receptors A and B, which are receptor-guanylyl cyclases. Receptor activation causes vasodilatation and diuresis. ANP and BNP are primarily produced by the heart. In addition to its muscular pump function, the heart can be considered as an endocrine organ.

Endothelins are 21-amino acid vasoconstricting peptides. There are 3 isoforms: ET-1, -2 and -3. They are mainly produced by the endothelium and upon cleavage from their precursor, secreted out of endothelial cells. Once released, they bind to Gq coupled receptor on vascular smooth muscle and cause constriction. Endothelins, along with other factors, regulate vascular tone. Overexpression of endothelins is implicated in systemic hypertension, heart failure, pulmonary hypertension, etc.

Adrenomedullin (AM) is a vasodilator peptide discovered in 1993. It belongs to the calcitonin peptide family. Human AM gene encodes a prepropeptide of 185 amino acids. Preproadrenomedullin is processed by proteolytic cleavage on pairs of basic residues to form a number of peptides. Circulating AM includes a 53-amino acid inactive peptide, which is glycated and counts for 85% of total circulating AM, and a mature active amidated peptide (AM-2). AM reduces blood pressure and increases heart rate and contractility in rodent model by infusion. It also protects human cardiac and vascular cells in vitro by reducing oxidative stress and inhibiting apoptosis. Under some circumstances, AM mimicks ischemia and reperfusion.

Renin-angiotensin-aldosterone system regulates blood pressure and body fluid homeostasis. When blood volume is low, kidneys secrete renin, which cleaves angiotensinogen produced by liver into angiotensin I. Angiotensin I is subsequently cleaved by angiotensin converting enzyme (ACE) to angiotensin II (ATII). ATII causes vasoconstriction and stimulates aldosterone secretion from the adrenal cortex. Aldosterone increases sodium and water reabsorption by the kidneys. Consequently, blood volume is increased, as is blood pressure. Dysregulation of this system has been implicated in hypertension, kidney disease, and heart disease.

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