Before considering this particular process, it should be recalled that the appearance of renin-producing cells in the developing kidney follows a characteristic spatiotemporal pattern. Once a particular vessel segment has matured, renin expression is switched off, but the capability to reactivate renin expression is preserved.
In the mature kidney renin-expressing cells are therefore confined to the most distal portion of the preglomerular vascular tree. Cells of the preglomerular vessels still have the capability to retransform into renin-producing cells. They do so in a typical retrograde direction starting from the vascular pole back to arcuate or interlobar arteries.
It appears as if this phenotype switch is an all or nothing phenomenon, meaning that recruited renin-producing cells display a very similar ultrastructure to that of typical juxtaglomerular epithelioid cells.
It is probably more than the activation of the renin gene as indicated by the observation that also the expression patterns of smooth muscle filaments 7 and of connexins change 93 with the phenotype. Well-known situations that lead to retrograde recruitment of renin-producing cells along the vessel wall are situations in which the renal perfusion pressure falls. It appears not unlikely therefore that the renal baroreceptor mechanisms not only regulate acute renin secretion but also the long-term transformation of vascular smooth muscle cells into renin producers.
Well-known situations that lead to a hypertrophy of the juxtaglomerular apparatus are salt losing diseases 91 , 95 or the abuse of diuretics. It is not unlikely that the enhanced formation of intrarenal prostaglandin E 2 in these situations is a major trigger for the switch on of renin expression in extraglomerular mesangial cells.
Pharmacological inhibition 98 , 99 or genetic interruption of the RAAS , also leads to compensatory increases in the number of renin-producing cells and in consequence of renin secretion, and this thwarts to some extent the intended blockade the RAAS.
It appears as if the magnitude of compensatory increase in renin secretion depends on the degree of RAAS inhibition. It is probably not a direct effect of ANG II that influences the phenotypic switch underlying the appearance or disappearance of renin-producing cells but rather the functional consequences of ANG II action such as changes in blood pressure and salt balance. Even years after its discovery renin still is a demanding molecule.
The main physiological regulators of renal renin synthesis and secretion, such as the SNS, prostaglandins, blood pressure, and extracellular volume have been identified, but their mode of action at the level of renin-producing cells is still less understood. It is well established that the number of renin-producing cells in the kidney is variable, depending on demand, but the understanding of the molecular events that lead to a reversible transformation of renal vascular smooth muscle cells into renin-producing cells is still at its beginning.
Open questions exist also about the physiological meaning of circulating prorenin, which reaches higher levels in the circulation than renin itself, at least in human subjects. Progress made by the generation of suitable genetically engineered mice as well as promising sophisticated gene profiling analyses of renin-producing cells raise hope that open fundamental questions will receive an answer in the near future.
The author thanks Hayo Castrop for critical reading and for helpful discussions. This study was supported by German research Foundation. Nguyen G. Renin, pro renin and receptor: an update. Clin Sci ; : — Google Scholar. Ingelfinger JR. Angiotensin-converting enzyme 2: implications for blood pressure and kidney disease.
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When afferent arteriole pressure is reduced, glomerular filtration decreases, and this reduces NaCl in the distal tubule. This serves as an important mechanism contributing to the release of renin when there is afferent arteriole hypotension, which can be caused by systemic hypotension or narrowing stenosis of the renal artery that supplies blood flow to the kidney.
When renin is released into the blood, it acts upon a circulating substrate, angiotensinogen , that undergoes proteolytic cleavage to form the decapeptide angiotensin I. Vascular endothelium, particularly in the lungs, has an enzyme, angiotensin converting enzyme ACE , that cleaves off two amino acids to form the octapeptide, angiotensin II AII , although many other tissues in the body heart, brain, vascular also can form AII.
The renin-angiotensin-aldosterone pathway is not only regulated by the mechanisms that stimulate renin release, but it is also modulated by natriuretic peptides released by the heart. These natriuretic peptides acts as an important counter-regulatory system. Therapeutic manipulation of this pathway is very important in treating hypertension and heart failure. ACE inhibitors , AII receptor blockers and aldosterone receptor blockers , for example, are used to decrease arterial pressure, ventricular afterload, blood volume and hence ventricular preload, as well as inhibit and reverse cardiac and vascular hypertrophy.
Cardiovascular Physiology Concepts Richard E. Klabunde, PhD.
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