Individuals with diabetes mellitus and hypertension display abnormal production of NO. In diabetes, excessive renal NO production can lead to glomerular hyperfiltration and damage to the glomerulus. Elevated levels of NO increase glomerular capillary pressure by reducing resistance in the afferent arteriole, causing hyperfiltration and subsequent glomerular damage. Normally, an increase in dietary salt intake stimulates renal NO production, which prevents an increase in blood pressure. However, in some individuals, NO production does not appropriately increase in response to elevated salt intake, resulting in elevated blood pressure.

Endothelin, a potent vasoconstrictor, is secreted by endothelial cells of the renal vessels, mesangial cells, and distal tubular cells in response to angiotensin II, bradykinin, epinephrine, and endothelial shear stress. Endothelin causes significant vasoconstriction of the afferent and efferent arterioles, leading to decreased GFR and RBF. Although endothelin may not affect GFR and RBF in resting subjects, its production is elevated in various glomerular disease states associated with diabetes mellitus.

Kallikrein, a proteolytic enzyme produced in the kidneys, cleaves circulating kininogen to bradykinin. Bradykinin, a vasodilator, stimulates the release of NO and prostaglandins, increasing RBF and GFR.

Hemorrhage activates renal sympathetic nerve activity and stimulates the production of angiotensin II. This process leads to constriction of renal arterioles and subsequent tubular sodium and water reabsorption, resulting in reduced RBF and GFR.

Adenosine, produced within the kidneys, constricts the afferent arteriole, thereby decreasing RBF and GFR. Adenosine plays a crucial role in tubuloglomerular feedback.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are secreted by the cardiac atria and ventricle, respectively, in response to expanded extracellular fluid volume and increased myocardial wall tension. Both ANP and BNP dilate the afferent arteriole and constrict the efferent arteriole, resulting in a modest increase in GFR with minimal change in RBF.

ATP, released by cells into the renal interstitial fluid, can have bidirectional effects on both RBF and GFR. Under certain conditions, ATP constricts the afferent arteriole, reducing RBF and GFR, and may contribute to tubuloglomerular feedback. Under other conditions, ATP may stimulate NO production and have opposing effects, increasing both RBF and GFR.

Administration of therapeutic doses of glucocorticoids increases GFR and RBF.

During the resting state and in the presence of inflammation and injury, the local release of histamine modulates RBF. Histamine decreases resistance in the afferent and efferent arterioles, resulting in increased RBF without significant elevation of GFR.

The proximal tubule of the kidney produces the vasodilator substance dopamine. Dopamine has several actions within the kidney, including increasing RBF and inhibiting renin secretion.
Abnormal production of NO is observed in individuals with diabetes mellitus and hypertension. Excess renal NO production in diabetes may be responsible for glomerular hyperfiltration (i.e., increased GFR) and damage to the glomerulus, problems characteristic of this disease. Elevated NO levels increase glomerular capillary pressure secondary to a fall in resistance of the afferent arteriole. The ensuing hyperfiltration is thought to cause glomerular damage. The normal response to an increase in dietary salt intake includes stimulation of renal NO production, which prevents an increase in blood pressure. In some individuals, however, NO production may not increase appropriately in response to an elevation in salt intake, so blood pressure rises.
Endothelin is a potent vasoconstrictor secreted by endothelial cells of the renal vessels, mesangial cells, and distal tubular cells in response to angiotensin II, bradykinin, epinephrine, and endothelial shear stress. Endothelin causes profound vasoconstriction of the afferent and efferent arterioles and decreases GFR and RBF. Although this potent vasoconstrictor may not influence GFR and RBF in resting subjects, production of endothelin is elevated in a number of glomerular disease states (e.g., renal disease associated with diabetes mellitus).
Kallikrein is a proteolytic enzyme produced in the kidneys. Kallikrein cleaves circulating kininogen to bradykinin, which is a vasodilator that acts by stimulating the release of NO and prostaglandins. Bradykinin increases RBF and GFR.
600 SECTION7Berne & Levy Physiology • Fig. 33.22 Pathway by which hemorrhage activates renal sympathetic nerve activity and stimulates production of angiotensin II. (Modified from Vander AJ. Renal Physiology. 2nd ed. New York: McGraw-Hill; 1980.) Hemorrhage ˜ Arterial blood pressure ˜ RBF and GFR (Intrarenal receptors) ° Renin secretion ° Plasma and renal renin ° Activity of renal sympathetic nerves ° Plasma and renal angiotensin II ° Constriction of renal arterioles Carotid sinus and aortic arch reflexes ° Tubular sodium and water reabsorption ˜ Renal excretion of sodium and water
Adenosine is produced within the kidneys and causes vasoconstriction of the afferent arteriole, thereby reducing RBF and GFR. As previously mentioned, adenosine plays an important role in tubuloglomerular feedback.
Secretion of atrial natriuretic peptide (ANP) by the cardiac atria and brain natriuretic peptide (BNP) by the cardiac ventricle increases when ECFV is expanded and myocardial wall tension is increased. Both ANP and BNP dilate the afferent arteriole and constrict the efferent arteriole. Therefore ANP and BNP produce a modest increase in GFR with little change in RBF.
Cells release ATP into the renal interstitial fluid. ATP can have bidirectional effects on both RBF and GFR. Under some conditions, ATP constricts the afferent arteriole, reduces RBF and GFR, and may play a role in tubuloglomerular feedback. Under other conditions, ATP may stimulate NO production and have directionally opposite effects, increasing both RBF and GFR.
Administration of therapeutic doses of glucocorticoids increases GFR and RBF.
Local release of histamine modulates RBF during the resting state and during inflammation and injury. Histamine decreases the resistance of the afferent and efferent arterioles and thereby increases RBF without elevating GFR.
The proximal tubule produces the vasodilator substance dopamine. Dopamine has several actions within the kidney, such as increasing RBF and inhibiting renin secretion.