This paper examines the physiological mechanisms that regulate arterial blood pressure and osmotic pressure in mammals, with emphasis on the renin-angiotensin-aldosterone system (RAAS). The paper describes how the nervous system, cardiovascular system, kidneys, and endocrine system work in concert to detect and respond to changes in blood pressure and electrolyte content. It details the cascade of enzymatic reactions that convert angiotensinogen to angiotensin II, explains the opposing effects of AT1 and AT2 receptor activation, and discusses the role of aldosterone and anti-diuretic hormone in regulating fluid balance. The paper also explores an alternate pathway involving angiotensin (1-7) that provides a counterregulatory mechanism against angiotensin-mediated hypertension.
Arterial blood pressure (BP) is under tight control by the mammalian nervous system, cardiovascular system, kidneys, and endocrine system (Vivas et al., 2014). The VII, IX, and X cranial nerves conduct peripheral taste, osmo-sodium, volume, and baroreceptor information to the solitary tract, while distinct bundles of neurons in the lamina terminalis respond to changes in plasma and cerebrospinal fluid sodium levels, osmolality, and angiotensin II levels. The information received is transmitted to the median preoptic, supraoptic, paraventricular, lateral parabrachial, and dorsal raphe nucleus for integration. The neurotransmitter systems involved include angiotensin, vasopressin, oxytocin, and serotonin.
The overall response to reductions in blood pressure and electrolyte content of bodily fluids is to trigger the sympathetic nervous system, endocrine system, and appropriate behavior to correct the deficiency (Vivas et al., 2014). This coordinated activation demonstrates how the brain integrates sensory information and orchestrates a systemic response, spanning from neural signaling to hormonal release and behavioral adjustment.
The most important arm of blood pressure control is the renin-angiotensin-aldosterone system, which mediates both short-term and long-term blood pressure regulation (Chopra, Baby, and Jacob, 2011). Plasma angiotensinogen, a 453-amino acid protein, is produced by the liver and enzymatically cleaved by renin to produce the 10-amino acid peptide angiotensin I, which induces mild vasoconstriction. Renin is produced by the juxtaglomerular cells in response to baroreceptor activation due to low blood pressure, detection of low sodium levels in the macula densa ultrafiltrate, and sympathetic nervous system activation (Farrao, Lara, and Lowe, 2014).
Angiotensin I can be further cleaved by angiotensin converting enzyme-1 (ACE1), primarily in the lungs, to produce the 8-amino acid angiotensin II, which induces arterial constriction and a measurable increase in blood pressure. Angiotensin converting enzyme-1 also inactivates bradykinin, further promoting an increase in blood pressure (Duka et al., 2006). This enzymatic cascade represents a finely tuned amplification system: successive enzymatic steps progressively concentrate and potentiate the signaling molecule, allowing a small trigger (low blood pressure) to produce a large physiological response.
Angiotensin II mediates its effects through two receptors, AT1 and AT2, each producing opposing activities (Chopra, Baby, and Jacob, 2011). Activation of AT1 induces vasoconstriction, anti-diuresis, anti-natriuresis, cell growth, and proliferation, while activation of AT2 results in vasodilation, diuresis, natriuresis, and anti-proliferation. Although both receptors can be found in tissues throughout the body, the control of blood pressure and the content of body fluids are mediated primarily by receptors expressed in the kidneys (Farrao, Lara, and Lowe, 2014).
Angiotensin II will also stimulate anti-diuretic hormone release from the pituitary, thereby promoting increased water reabsorption in the renal collecting ducts. It induces aldosterone production from the adrenal cortex, promotes sodium reabsorption in the kidneys, and enhances potassium and hydrogen excretion through the kidneys. The importance of the kidneys in controlling blood pressure is highlighted by the fact that this organ produces angiotensinogen, ACE, renin, and angiotensin II at high levels locally, creating a self-contained regulatory unit within the kidney itself.
"Counterregulatory mechanism protecting against hypertension"
You’re 82% through this paper. Sign up to read the remaining 1 section.
Sign Up Now — Instant Access Already a member? Log inAlways verify citation format against your institution’s current style guide requirements.