ATP Bradykinin ↑ Prostaglandins, ↓ ACE ↑↑ Natriuretic peptides (ANP, BNP) ↑ ECFV ↑ No change
A-II, angiotensin II; ACE, angiotensin-converting enzyme; ECFV, extracellular fluid volume.
Tubuloglomerular feedback (TGF) is absent in mice that do not express the adenosine receptor (A1). This underscores the importance of adenosine signaling in TGF. Studies have shown that when GFR increases and causes the concentration of NaCl in tubular fluid at the macula densa to rise, more NaCl enters cells via the 1Na+-1K+-2Cl− symporter (NKCC2) located in the apical plasma membrane (see
Fig.
33.20 ). Increased intracellular [NaCl] in turn stimulates release of ATP via ATP-conducting ion channels located in the basolateral membrane of macula densa cells. In addition, adenosine production is also enhanced. Adenosine binds to A1 receptors and ATP binds to P2X receptors located on the plasma membrane of smooth muscle cells in the afferent arteriole. Both hormones increase intracellular [Ca++], which causes vasoconstriction of the afferent artery and therefore a fall in GFR. Although adenosine is a vasodilator in most other vascular beds, it constricts the afferent arteriole in the kidney.
binding to α1-adrenoceptors, which are located mainly in afferent arterioles. Activation of α1-adrenoceptors decreases RBF and GFR. Dehydration or strong emotional stimuli (e.g., fear, pain) also activate sympathetic nerves and reduce RBF and GFR.
Angiotensin II is produced systemically as well as locally within the kidneys. It constricts the afferent and efferent arterioles and decreases both RBF and GFR.
Fig. 33.22 shows how norepinephrine, epinephrine, and angiotensin II act together to decrease RBF and GFR and thereby dThe efferent arteriole is more sensitive than the afferent arteriole to angiotensin II. Therefore with low concentrations of angiotensin II, constriction of the efferent arteriole predominates, and GFR increases and RBF decreases. However, with high concentrations of angiotensin II, constriction of both afferent and efferent arterioles occurs, and GFR and RBF both decrease (see
Fig. 33.21
Individuals with renal artery stenosis (narrowing of the lumen of the artery) caused by atherosclerosis, for example, often have elevated systemic arterial blood pressure mediated by the renin-angiotensin system. Pressure in the renal artery proximal to the stenosis is increased, but pressure distal to the stenosis is normal or reduced. Autoregulation is important in maintaining RBF, PGC, and GFR in the presence of this stenosis. Administration of drugs to lower systemic blood pressure also lowers the pressure distal to the stenosis; accordingly, RBF, PGC, and GFR fall.
Significant hemorrhage decreases ECFV and arterial blood pressure and therefore activates sympathetic innervation of the kidneys via the baroreceptor reflex (