Arterioles, renal

In the kidney, ANG II reduces renal blood flow and constricts preferentially the efferent arteriole of the glomerulus with the result of increased glomerular filtration pressure. ANG II further enhances renal sodium and water reabsorption at the proximal tubulus. ACE inhibitors thus increase renal blood flow and decrease sodium and water retention. Furthermore, ACE inhibitors are nephroprotective, delaying the progression of glomerulosclerosis. This also appears to be a result of reduced ANG II levels and is at least partially independent from pressure reduction. On the other hand, ACE inhibitors decrease glomerular filtration pressure due to the lack of ANG II-mediated constriction of the efferent arterioles. Thus, one important undesired effect of ACE inhibitors is impaired glomerular filtration rate and impaired kidney function. 

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

Proximal tubule cells are exquisitely sensitive to vasculat disturbances and acute tubular necrosis (ATN) can occur naturally in areas of poor perfusion resulting from falling blood pressure, or vasospasm of renal vessels or arterioles. In other words hypoxia associated with partial ischaemia can cause severe damage. It is not then surprising that anoxia associated with iatrogenic, surgically induced total ischaemia produces irreversible damage within a short time unless steps are taken to prevent it. 

Glomerular capillary pressure is determined primarily by renal blood flow (RBF). As RBF increases, PGC and therefore GFR increase. On the other hand, as RBF decreases, PGC and GFR decrease. Renal blood flow is determined by mean arterial pressure (MAP) and the resistance of the afferent arteriole (aff art) ... 

An overall increase in sympathetic nerve activity includes an increase in sympathetic input to the kidneys. Consequently, resistance of the afferent arteriole increases, leading to a decrease in RBF. As discussed, this results in a decrease in PGC, GFR, and urine output. As such, the renal excretion of sodium and water is decreased. In other words, sodium and water are... 

Angiotensin II. Angiotensin II also increases the resistance of the renal arterioles and consequently decreases RBF and GFR. Angiotensin II is synthesized by the following pathway ... 

T Resistance of afferent arteriole —> 4 renal blood flow — 4 glomerular filtration rate -4 4 Na+ filtration... 

Acute renal failure is a rare but serious side effect of ACE inhibitors preexisting kidney disease increases the risk. Bilateral renal artery stenosis or unilateral stenosis of a solitary functioning kidney renders patients dependent on the vasoconstrictive effect of angiotensin II on efferent arterioles, making these patients particularly susceptible to acute renal failure. 

Three generally accepted mechanisms are involved in the regulation of renin secretion (Fig. 18.2). The first depends on renal afferent arterioles that act as stretch receptors or baroreceptors. Increased intravascular pressure and increased volume in the afferent arteriole inhibits the release of renin. The second mechanism is the result of changes in the amount of filtered sodium that reaches the macula densa of the distal tubule. Plasma renin activity correlates inversely with dietary sodium intake. The third renin secretory control mechanism is neurogenic and involves the dense sympathetic... 

Nephrotoxicity is the most common and the most serious long-term toxicity of amphotericin B administration. This drug reduces glomerular and renal tubular blood flow through a vasoconstrictive effect on afferent renal arterioles, which can lead to destruction of renal tubular cells and disruption of the tubular basement... 

Vasopressin occurs in two variations arginine-vasopressin (AVP) and lysine-vasopressin (LVP), in which Arg is replaced by Lys. The conformation of these hormones is almost identical to that of oxytocin, except that the terminal tail is con-formationally free and not held by the ring. The physiological role of the vasopressins is the regulation of water reabsorption in the renal tubules (i.e., an antidiuretic action). In high doses, they promote the contraction of arterioles and capillaries and an increase in blood pressure hence the name of these hormones. Because of their very similar structures, OT and VP overlap in a number of effects. 

Minoxidil is a very efficacious orally active vasodilator. The effect results from the opening of potassium channels in smooth muscle membranes by minoxidil sulfate, the active metabolite. Increased potassium permeability stabilizes the membrane at its resting potential and makes contraction less likely. Like hydralazine, minoxidil dilates arterioles but not veins. Because of its greater potential antihypertensive effect, minoxidil should replace hydralazine when maximal doses of the latter are not effective or in patients with renal failure and severe hypertension, who do not respond well to hydralazine. 

The renal vascular receptor functions as a stretch receptor, with decreased stretch leading to increased renin release and vice versa. The receptor is apparently located in the afferent arteriole, possibly in the juxtaglomerular cells. Stretch-induced changes in renin release are mediated by changes in Ca2+ concentration in the juxtaglomerular cells. 

The hypertension itself damages renal arterioles, which become hypertrophied and narrowed. Thus, organic renal ischemia results, in itself causing continuous production of pressor substances. 

Under the proper stimulus renin is released into the circulating blood where it can be identified, especially in that from the renal vein. It acts rapidly upon its specific substrate, splitting the protein into peptides, one or more of which have been called hypertensin or angiotonin. Hypertensin has been concentrated but not obtained in pure form. It is the effector substance of renin, constricting arterioles and raising blood pressure. The action of hypertensin is abolished by hypertensinase, an enzyme found in blood and renal extracts. Fortunately, the latter is destroyed by heat and alkalinity. 

An interesting reaction to intradermal histamine has been described (55), which, while not a pressor substance, appears to reproduce certain symptoms and signs encountered in hypertensive subjects. Histamine has a renal action similar to epinephrine (47), constricting efferent arterioles. In neurogenic hypertensive patients it also produces the hypertensive diencephalic syndrome." Whether this reaction is direct, or indirect through some other mechanism, is obscure. 

An antihypertensive substance is one which does not affect blood volume, blood viscosity, or the function of the heart it lowers blood pressure to normal levels in hypertensive states by generalized arteriolar dilatation, including those of the kidneys. Vasodilators (such as histamine), which lower arterial pressure at the expense of renal blood flow, are not antihypertensive. Furthermore, an ideal substance should affect the blood pressure in normal states to little or no extent. It can be predicted, however, that when true antihypertensive substances are found, they will not increase or maintain renal blood flow in the face of lowered arterial pressure when renal arterioles have lost the ability to dilate because of pathological changes (see Figure 3). 

---