myogenic mechanism

**Mechanism:** Increased arterial pressure stretches the vessel wall, which opens stretch-activated (mechanosensitive) cation channels. This depolarizes vascular smooth muscle cells, opens voltage-gated L-type Ca2+ channels, and raises intracellular Ca2+. Ca2+ binds calmodulin and activates myosin light chain kinase (MLCK), which causes vasoconstriction. Decreased pressure does the opposite and causes vasodilation. Because the vessel constricts in response to pressure, resistance rises as pressure rises, so flow stays roughly constant (Q = ΔP/R).

**Renal autoregulation:** - Renal blood flow (RBF) and GFR stay constant over a mean arterial pressure of about 80-180 mmHg. - The myogenic response occurs mainly in the afferent arteriole. It is fast (onset in seconds) and protects the glomerulus from barotrauma during pressure surges. - It works together with tubuloglomerular feedback (TGF). TGF is slower and is mediated by macula densa NaCl sensing and adenosine-mediated afferent constriction. - Autoregulation is not neural or hormonal. It persists in a denervated or isolated kidney, such as a transplanted kidney.

**Other vascular beds:** The myogenic response also contributes to autoregulation in the brain (cerebral autoregulation, MAP ~60-150 mmHg), the heart (coronary), and skeletal muscle. Metabolic factors (CO2, H+, adenosine, K+, O2) usually dominate in the brain, heart, and skeletal muscle. The myogenic mechanism is more dominant in the kidney.

**Clinical significance:** - **Hypotension or shock** (MAP below ~80): autoregulation fails, so GFR falls and prerenal AKI can result. - **NSAIDs** block prostaglandin-mediated afferent dilation, which impairs autoregulation. In volume-depleted patients, this can cause AKI. - **ACE inhibitors/ARBs** dilate the efferent arteriole. In a patient with bilateral renal artery stenosis or volume depletion, they drop GFR. - **Chronic hypertension** shifts the autoregulatory curve to the right. This protects the glomerulus but also means the patient tolerates abrupt BP lowering poorly (risk of ischemia). - **Calcium channel blockers** (dihydropyridines like amlodipine, nifedipine) block L-type Ca2+ channels, which blunts the myogenic response and dilates the afferent arteriole. - **Diabetes:** Impaired afferent constriction in early diabetes transmits systemic pressure to the glomerulus. This contributes to hyperfiltration and glomerular injury.

**High-yield contrast:** - Myogenic = responds to pressure/stretch (intrinsic to smooth muscle). - Tubuloglomerular feedback = responds to distal tubular NaCl delivery at the macula densa. - Metabolic autoregulation = responds to local metabolites (more important in brain, heart, muscle). - Neurohumoral control (sympathetic, angiotensin II, ANP, etc.) is separate from autoregulation.

**Related concept:** The Bayliss effect is another name for the myogenic response, named after William Bayliss.