Renal Autocoids and Hormones

Renin-Angiotensin System

renin produced by JG cells (stim through high cAMP; inhib by increased intracellular calcium)

also produced in brain, vasculature, uterus, salivary glands

renin cleaves angiotensinogen to angiotensin I; ACE (angiotensin converting enzyme) converts to AII

can also be converted to AIII (active in adrenal glands; little vasoconstrictor activity)

renin release: decreased perfusion pressure; decreased plasma vol; decreased macula densa NaCl; increased prostaglandins; increased beta adrenergic stim

renin inhibition: increased perfusion pressure; increased plasma vol; increased MD NaCl; NSAIDs; AII

effects: vasoconstriction (increases TPR; decreases RBF); increases proximal Na reabsorption; increases aldosterone synth; increases thirst and Na appetite

more dominant vasoconstriction at efferent, so GFR remains constant despite decreased RBF

leads to increased filtration fraction

normal: AII protects blood pressure and plasma volume through vasoconstriction and Na reabsorption

pathologic (CHF, hypertension): AII levels become elevated, ACE inhibitors used to treat

Aldosterone

mineralcorticoid synthesized by zona glomerulosa cells of adrenal cortex

release stimulated by AII, ACTH, high plasma K

binds to transcription factors in late distal tubule and collecting duct

facilitates more NaK-ATPase and thus Na reabsorption
electroneutrality maintained by H (intercalated) and K (principal) secretion

excess: Na reabsorption, ECFV and plasma vol expansion, hypertension, hypokalemia, met alkalosis

‘aldosterone escape’ - high aldosterone balanced by increased prox tubule Na excretion after a few days

deficiency: hyperkalemia, vol depletion, hypotension

ADH (vasopressin)

peptide produced in hypothalamus and stored in pituitary

binds to V₁ in glomerulus mesangial cells and vascular smooth muscle when in high concentrations

causes vasoconstriction via phopholipase C

binds to V₂ in cortical and medulary collecting tubules when in low conc

cAMP leads to APQ-2 water channel vesicle insertion into apical membrane
APQ-3 channels in basolateral side facilitate water to move down conc gradient out of tubule

excess: hyponatremia

deficiency: hypernatremia (diabetes insipidus)

Eicosinoids (Prostaglandins, Thromboxane, Leukotrienes)

autocoids produced from arachadonic acid

cyclooxygenase leads to prostaglandins and thromboxane (inhibited by NSAIDs)
lipoxygenase leads to leukotrienes

prostaglandin synth stim by: AII, norepi, ADH, renal ischemia

PGE₂ and PGI₂ maintain GFR and RBF during actions of AII, especially in pathalogic states when there is an abnormally high AII, catacholamines or ADH
NSAIDs in this case could result in rapid decrease in GFR

actions

Increase: PGE₂ and PGI₂
Decrease: TxA₂ and LTC₄

Renal blood flow

Increase: PGE₂ and PGI₂
Decrease: TxA₂ and LTC₄

NaCl excretion

Increase: PGE₂ > PGI₂

H₂O excretion

Increase: PGE₂ > PGI₂

Renin secretion

Increase: PGE₂ > PGI₂

prostaglandins basically help balance vasoconstrictors to avoid decreased GFR and renal ischemia

Nitric Oxide

synth catalized by NO synthase; short half life; diffuses to nearby tissues

leads to vasodilation via cGMP

many drugs and hormones (ACh, histamine, seratonin, nitrogylcerine) stimulate NO production

may have a role in tubuloglomerular feedback

Endothelin (opposes of Angiotensin-II)

potent vasoconstrictors; three isoforms (ET-1, ET-2, ET-3)

ET-1 produced by endothelial cells

half life only minutes, but effects last hours

action through phospholipase C

causes decreased GFR and decreased Na reabsorption

Atrial Natriuretic Peptide (opposes of aldosterone)

synth and released by atria in response to increased atrial pressure (volume expansion)

causes vasodilation in vasculature and kidney via cGMP

dilates primarily afferent arterioles, so increases GFR

reduces Na reabsorption in medullary collecting tubule

supresses renin secretion so increases Na excretion

Erythropoietin

synthesized in peritubular caps of kidney and in liver of fetus

stimulates RBC production in response to decreased oxygen pressure or hemoglobin conc

deficiency: anemia; can be helped by subcutaneous injection

excess: polycythemia (renal tumors, renal cysts, polycystic kidney disease, renal artery stenosis)