Exam 5 Review:  Chapter 25:  Regulation I:  Renin-Angiotensis and Autoregulation

renin-angiotensin system - A complex endocrine negative feedback control system which plays important role in regulating blood volume, arterial pressure, and cardiac and vascular function; in response to sympathetic stimulation, low blood pressure or low blood sodium levels, (1) the juxtaglomerular apparatus of the kidney will release the enzyme renin, (2) renin will catalyze the activation of an inactive precursor substance, angiotensinogen, which is made by the liver, into angiotensin I, (3) angiotensin I (which has some activity of its own) will be further activated by an enzyme found in the lungs, angiotensin-converting enzyme (ACE), into active angiotensin II, (4) angiotensin I & II stimulate these physiological responses:  (a) enlargement of the heart and blood vessels, (b) systemic vasoconstriction, (c) aldosterone release from the adrenal cortex, (d) activation of the hypothalamic thirst center, (e) ADH release from the posterior pituitary/neurohypophysis; processes (c, d, and e) cause retention of salt and water by the kidneys and as a result, increased blood volume; thus this system has a powerful hypertensive effect.

renin - The enzyme released by the juxtaglomerular cells of the juxtaglomerular apparatus of the nephron in response to the detection of decreased filtrate flow and decreased filtrate osmolality in the distal convoluted tubule by the macula densa cells; this enzyme is released into the bloodstream where it finds its substrate, angiotensinogen, and converts it into angiotensin I, a moderately effective hypertensive control substance, but more importantly, the precursor substrate to angiotensin II.

angiotensinogen - A peptide synthesized in the liver which is released into the bloodstream to be the substrate for the enzyme renin which converts it to angiotensin I, a moderately effective hyperensive control substance, but more importantly angiotensin I is, itself, the precursor to angiotensin II [See ACE]; these vasoactive peptide products can also stimulate aldosterone release from the adrenal cortex, ADH/vasopressin from the posterior pituitary, and stimulate the hypothalamic thirst center.

angiotensin converting enzyme (ACE) - The enzyme released by certain cells of the lungs, kidney and systemic blood vessels which catalyzes the conversion of its substrate, angiotensin I, a moderately effective hypertensive control substance, into the more physiologically potent angiotensin II; elevations of this enzyme are detected in a variety of diseases and contribute to hypertension in those affected; drugs which inhibit this enzyme are used to treat hypertension and congestive heart failure.

angiotensin I - The peptide product of the circulating enzyme renin which converts the inactive precursor angiotensinogen to angiotensin I, a moderately effective hypertensive regulatory substance, but more importantly, the precursor to angiotensin II.

angiotensin II - The peptide product of the lung enzyme angiotensin-converting enzyme (ACE) which converts the angiotensin I into angiotensin II, a highly effective hypertensive regulatory substance which targets the adrenal cortex for aldosterone release, the anterior pituitary for ADH/vasopressin release, the hypothalamic thirst center, and the smooth muscle in arterial walls for contraction.

renal autoregulation - A series of local mechanisms (independent of the nervous system) which control local renal blood flow and blood pressure to insure adequate blood supply to the glomeruli and renal capillary beds in the face of systemic blood pressure changes:  (1) myogenic control - A localized smooth muscle cellular reflex in which the stimulus of stretching in the smooth muscles in the walls of small arterioles (as a result of increased blood pressure to the region) causes an immediate response causing vasoconstriction of the afferent arterioles and a decrease in blood flow to the glomeruli and, thus, a decrease in GFR [and vice versa, to increase GFR]; (2) tubuloglomerular control - macula densa cells in the juxtaglomerular apparatus respond to decreased filtrate flow and decreased filtrate osmolality release a local hormone causing vasodilation of the afferent arterioles and an increase in blood flow to the glomeruli and, thus, an inecrease in GFR [and vice versa, to decrease GFR].  [Note:  the response of the macula densa cells to decreased filtrate flow and decreased filtrate osmolality also causes the macula densa cells to signal to the juxtaglomerular cells to release renin to activate the renin-angiotensin system.]

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