Blood flow afferent arteriole effects

Renal blood flow has a direct effect on GFR, which in turn has a direct effect on urine output. As RBF increases, GFR and urine output increase. Conversely, as RBF decreases, GFR and urine output decrease. Furthermore, any change in urine output affects plasma volume and blood pressure. Therefore, the regulation of RBF and GFR are important considerations. According to Ohm s law (Q = AP/R), RBF is determined by mean arterial pressure (MAP) and the resistance of the afferent arteriole (Raffart) ... 

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... 

Blood flow to the two kidneys is approximately 22-25% of the cardiac output. The kidneys are supplied by the renal artery which enters the kidneys through the hilum and then branches progressively to form the interlobar arteries, arcuate arteries, interlobular arteries (also called radial arteries), and afferent arterioles, which lead to the glomerular capillaries. The distal ends of each glomerulus coalesce to form the efferent arteriole, which leads to a secondary capillary network, the peritubular capillaries which surround the renal tubules. The cortex receives approximately 90% of the blood flow compared to the medulla or papillae so blood-borne toxic molecules reaching the kidneys have a more toxic effect on the cortex, as compared to the medulla or renal papillae. The interstitial space is occupied by the fenestrated peritubular capillaries and a small number of fibroblast-like cells. Increase in thickness of interstitial space in pathological conditions is due to edema, proliferation of fibrous tissue, or infiltration of inflammatory cells (Guyton and Hall, 2006). 

Infusions of AmB, intravenously or into the renal artery, induce short-term reduction in renal blood flow (RBF) and GFR, and an increase in renal vascular resistance, in both rats and dogs [83-85]. The effects of short term infusions of AmB on the renal microcirculation in rats revealed that the single nephron GFR was decreased by 2 mechanisms (Table 1) 1) a decrease in single nephron plasma flow, due to vasoconstriction of the afferent and efferent arterioles, and 2) a reduction in the glomerular capillary ultrafiltration coefficient (Kf), an effect probably mediated by mesangial cell contraction [86]. Previous micropuncture studies demonstrated a similar vasoconstriction of the afferent arteriole but also an increased permeability of the tubular epithelium to inulin [75]. Thus, the reduction in GFR after acute AmB infusions can be attributed to contraction of afferent smooth muscle cells, efferent smooth muscle cells and glomerular mesangial cells, as well as increased tubular permeability with back-leak... 

Since acute DIN appears to be dose related, pharmacokinetic and pharmacodynamic monitoring is an important means of preventing toxicity. However, the persistent presence of therapeutic or low cyclosporine concentrations cannot preclude nephrotoxicity. Calcium channel blockers may antagonize the vasoconstrictor effect of cyclosporine by dilating glomerular afferent arterioles and preventing acute decreases in renal blood flow and glomerular filtration. Lastly, decreased doses of cyclosporine or tacrolimus, primarily when used in combination with other non-nephrotoxic immunosuppressants, may minimize the risk of toxicity, but this may increase the risk of chronic rejection. 

When infused intrarenally in animals, PAF decreases renal blood flow, glomerular filtration rate, urine volume, and excretion of Na without changes in systemic hemodynamics. These effects are the result of a direct action on the renal circulation. PAF exerts a receptor-mediated biphasic effect on afferent arterioles, dilating them at low concentrations and constricting them at higher concentrations. The vasoconstrictor effect appears to be mediated, at least in part, by COX products, whereas vasodilation is a consequence of the stimulation of NO production by endothelium. 

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