• animal experiments: Cross-Transplantation: rats with essential HTN had kidneys exchanged with normotensive rats
• normotensive became hypertensive and hypertensive became normotensive
• Goldblatt Experiment: various arteries in dogs were clamped closed and BP monitored
• only renal artery clipping resulted in a significant change in BP
• mechanism: ischemia Þ Ý renin Þ Þ Ý BP
• human disease: Kidney Transplant: patients with CRF due to essential HTN received transplants from normotensive donors
• recipient became normotensive
• Dialysis Patients: 80-90% of hypertensive ESRD patients can be brought to normal BP through dialysis
• the other 10-20% can be normalized with nephrectomy
• Hypertension is initiated by a decrease in salt excretion and maintained by an increased peripheral resistance:
• normal: BP = CO x TPR
• experiment: do a 5/6 nephrectomy on a dog, give a salt load and measure these parameters
• plasma volume and cardiac output initially rise, then fall to just above normal within a couple of days
• BP rises and plateaus at a new high level
• TPR initially falls and then increases and plateaus at a level higher than the initial TPR
• conclusion: HTN is initiated by Ý CO, but is maintained by Ý TPR
• important reminder: Ý TPR is not enough to cause sustained BP elevation unless Na⁺ excretion is compromised
• how? Þ see table for the main players
• basically all of the factors that Ý ECFV and act as pressors are increased in renal disease
• ß GFR also contributes by further facilitating salt retention
• kinins are reduced by renal disease
• these factors are modulated mainly by ANF and prostaglandins
• Factors that Affect Cardiac Output (volume)
• Ý ECFV (salt retention)
• aldosterone
• angiotensin II
• norepi
• ADH (via water, not Na)
• ß ECFV (salt excretion)
• ANF
• EDRF/NO
• Kinins
• PGE₂/PGI₂
• Factors that Affect Peripheral Resistance
• Pressors (constrict)
• AII
• endothelin
• norepi (SNS)
• ADH (vasopressin)
• Depressors (dilation)
• ANF
• EDRF/NO
• Kinins
• PGE₂/PGI₂

• prostaglandins are actually increased in renal disease, stimulated by increased renin and sympathetic tone
• PG serve to counteract the effects of renin/AII/aldo and SNS via vasodilation, but this is a double-edged sword because PG preferentially dilate the afferent arteriole; while this increases RBF and filtration fraction, restoring GFR; preferential afferent dilation results in higher glomerular capillary pressures which can lead to further renal damage
• ACE inhibitors have been shown to counteract this deleterious increase in P_cap effect by causing efferent dilation
• Ca⁺⁺ channel blockers may or may not have an effect
• NSAIDS are particularly dangerous in renal disease because they block PG synthesis and the pressors are unopposed

• autoregulation normally works to maintain GFR and RBF for mean arterial pressures of 80-180 mm Hg
• the main mechanism of autoregulation in the kidney is afferent arteriolar tone
• in renal disease, the afferent arteriole loses the ability to adapt and the autoregulation curve becomes more of a line
• the kidney loses ability to adapt and patients with kidney damage are much more sensitive to hypertensive damage

• 2-3% of essential hypertension is due to renovascular disease Þ leads to hypertension if disease is bilateral
• 70% of this is fibromuscular disease and is more common in white women <25 (you’re hosed Eiran!)
• 30% due to atherosclerotic disease; more common in older, male, smokers, linked to peripheral disease
• normalization of BP in diabetic nephropathy slows progression; data isn’t as strong for non-diabetic renal disease

Diagnosis:

• mainly a game of clinical suspicion Þ elevated BP in < 25 or > 55; abdominal bruit; refractory HTN
• labs: ultrasound, renal angiogram

• medical
• surgical revascularization
• angioplasty