Physiology 19: Role of Kidneys in Long-Term Control of Arterial Pressure and in Hypertension
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Sympathetic nervous system controls short-term arterial pressure
Rising pressure causes kidneys to excrete excess volume (renal-body fluid system) = pressure
diuresis and pressure natriuresis (double that of water)
o Renal urinary output curve or renal function curve: 50 mmHg and below -> urine output
is zero. 100 mmHg is normal and 200 mmHg, 6-8x normal.
 Equal increase in sodium output
o When nervous system blocked, kidney is sole regulator by increasing urine volume
(returns Q and BP to normal)
Water and salt output must equal intake. Occurs at equilibrium point at intersection of renal
output curve and net H2O and Na intake (~100mmHg)
o “Negative balance” of fluid (loss in urine) will not cease until pressure returns exactly to
equilibrium point. If fluid volume falls below, output will decrease to return it back to
equilibrium = near infinite feedback gain principle
As long as renal output (Na and H2O) and intake remain parallel, mean arterial pressure level
will readjust to 100 mmHg
o Alter by shifting pressure level of renal output OR change level of water and salt intake
(two primary determinants of long-term arterial pressure level)
 Impossible to change long-term mean arterial pressure level without changing
one of these. If changed, arterial pressure regulated at new pressure level
(where the 2 curves intersect)
Chronic change in arterial pressure have greater effect on renal output of Na and H2O than
acute change (chronic renal output curve is much steeper than acute curve)
o Increased pressure has direct effect on kidney to increase excretion, and indirect effect
by nervous and hormonal changes when BP is increased
 Increased BP increases sympathetics, angiotensin II and aldosterone (reduce
antinatriuretic systems)
o Large intake of Na and H2O to 6x normal have only small increase in BP (same with
decreases) -> salt insensitive
 Kidney injury (loss of nephrons) or excess antinatriuretic hormones -> salt
sensitive so greater increased in BP needed to raise renal output
 Long-term high salt intake may damage kidneys, too
Arterial pressure (AP) = Cardiac Output (Q) x Total Peripheral Resistance (TPR)
o Acute change in TPR raises AP immediately but not maintained (increased resistance
everywhere besides in the kidneys doesn’t change equilibrium point so pressure
diuresis/natriuresis return AP to normal)
 When TPR increases, also increases the intrarenal vascular resistance at same
time shifting renal function curve so TPR indirectly increases renal output via
increase in renal resistance
↑ ECF volume -> ↑ BV -> ↑ mean filling P -> ↑ venous return to heart -> ↑Q -> either direct ↑
AP or autoregulation (↑ TPR -> ↑ AP) -> ↑ urine output reducing ECF volume
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o Autoregulation = increased flow causes constriction of vessels -> ↑TPR
Increase in salt intake is more likely to elevate the arterial pressure than water (salt is main
determinant of ECF volume)
o Pure water excreted as rapidly as ingested
o Excess salt in ECF increases osmolality -> stimulates thirst center so fluid intake ↑ and
stimulates hypothalamic-posterior pituitary gland in increased ADH secretion
Hypertension = mean arterial pressure is greater than upper range of accepted norm (> 110
mmHg mean AP; normal = 90 mmHg)
o Mean pressure occurs when diastolic BP > 90 mmHg and systolic BP > 135 mmHg
o Causes excess heart workload (early failure and coronary heart disease), damages blood
vessels in brain (cerebral infarct aka stroke) and injures kidneys
o Volume-loading hypertension -> caused by excess accumulation of ECF in body
Reduction of kidney mass reduces ability to excrete salt and water (raise AP) -> volume-loading
hypertension
o Acute effect with high intake Na and H2O = ↑ ECF volume, blood volume and Q; AP rose
slower (initial decrease in TPR by baroreceptor mechanism but after adaptation AP rises)
o Longer effect -> progressive increase in TPR while Q decreased to normal (long term BF
autoregulation), ECF volume and blood volume returned to normal (increased TPR
decreased capillary P, fluid absorbed in blood; kidneys excrete fluid)
o Last effect -> hypertension, ↑ TPR, ECF and blood volume and Q normal
 So ↑ TPR is secondary to hypertension
Artificial kidney patients must maintain body fluid volume at normal or else hypertension
develops
Excess aldosterone or other steroids cause volume-loading hypertension
o Adrenal gland tumor = primary aldosteronism -> ↑ Na and H2O absorption
 Simultaneous salt intake increase worsens hypertension and may damage
kidney causing further Na and H2O retention (lethal)
Renin = released by kidneys when AP low
o Synthesized as prorenin by juxtaglomerular cells (in walls of afferent arterioles
immediately proximal to glomeruli)
o Renin acts on renin substrate (angiotensinogen) releasing angiotensin I which is
converted in endothelium of lungs by angiotensin converting enzyme -> angiotensin II
 Angiotensin II inactivated rapidly by angiotensinases, causes vasoconstriction
(esp in arterioles -> ↑ TPR) and ↓ excretion of salt and water
Renin-angiotensin system powerful enough to return AP to halfway normal after hemorrhage
(needs 20 mins to be fully active)
Angiotensin II acts directly on kidneys (Na and H20 retention) and causes aldosterone secretion
(indirect Na and H2O reabsorption)
o Constricts renal arterioles -> rapid reabsorption of fluid. Direct action on tubular cells
also reabsorbs Na and H2O. (more potent than indirect effect)
o Aldosterone increases Na reabsorption and subsequent H2O retention
Angiotensin promotes chronic elevation of AP
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Renin-angiotensin system is automatic feedback mechanism that helps maintain AP at or near
normal even when salt intake increases
Tumor of JG cells -> high renin, high angiotensin II, severe hypertension
“One-kidney” Goldblatt hypertension = one kidney removed and the other renal artery clamped
(or stenosed) -> early rise in AP (renin-angiotensin system) but then renal AP normal in 5-7 days
so less renin; second rise in AP from Na and H2O retention which is help at stable (but high)
level to maintain normal urine output
“Two-kidney” Goldblatt hypertension = one renal artery clamped (or stenosed) -> constricted
kidney secretes renin and retains Na and H2O (causes normal kidney to do the same because of
renin)
o Patchy ischemic kidney tissue secretes renin -> hypertension from diseased kidney
Coarctation of the aorta = 40-60% higher AP in upper body than lower body because lower BF in
kidneys causes renin to be secreted -> hypertension in upper body and normal in lower
o BF in arms and legs is normal though -> long-term autoregulation develops so nearly
completely so local BF mechanisms compensate
Preeclampsia (toxemia of pregnancy) = hypertension (from ischemic placenta releasing toxic
substances) -> endothelial dysfunction decreases release of NO and other vasodilators; also
thickened kidney glomerular membranes reduce GFR
Acute neurogenic hypertension = stimulation of sympathetic nervous system (excited, anxiety)
o May occur if nerves from baroreceptors cut or tractus solitaries destroyed -> sudden
reduction of AP signaled (resets in 2 days)
Early development of hypertension caused by more active sympathetic NS (increases
preglomerular renal arterial resistance and decreases glomerular membrane permeability)
o Monogenic hypertension = mutation of single gene cause excess Na and H2O
reabsorption (rare, <1% of hypertensive cases)
Primary (Essential) Hypertension = 90-95% of cases; hypertension of unknown origin (excess
weight gain and sedentary lifestyle)
o Increase physical activity and weight loss first step in treating hypertension
o Q is increased (extra adipose tissue, ↑ metabolic rate), sympathetic nerve activity
increased in obesity (leptin stimulates hypothalamus exciting vasomotor centers),
angiotensin II and aldosterone levels increased in obesity, renal-pressure natriuresis
impaired so higher AP needed to excrete Na and H2O
o Drugs:
 Vasodilator drugs = inhibit symapthetics to kidneys, directly relax renal smooth
muscles or block renin-angiotensin action on kidney
 Natriuretic/diuretic drugs = block Na active transport
Sodium-loading renal function curves -> AP increases slowly by increasing Na intake (used for
essential hypertensive patients)
o Salt-insensitive hypertension = no increase in AP with increased Na intake
o Salt-sensitive hypertension = increased Na exacerbates hypertension; may be with loss
of nephrons or normal aging
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Salt sensitivity is not all-or-none (paradigm) and not fixed (more sensitive with
age)
First line of defense in acute AP change = nervous system control; second line defense = kidneys
o Rapidly acting pressure control mechanisms: baroreceptor feedback, CNS ischemia,
chemoreceptor mechanisms -> ↑ vein and arteriole constriction, HR and contractility of
heart (within seconds)
o Pressure control mechanisms after few minutes: renin-angiotensin, stress-relaxation of
vasculature, and capillary fluid shift mechanism (30 mins)
o Long-term pressure control mechanisms: renal-blood fluid pressure control (few hours)
 Decreased pressure increases aldosterone within minutes