This is a schematic rapresentation of phisiology of arterial blood pressure control.
Nervou sistem, cardiac function, hormonal regulation mechanisms, kidney funcion are involved.
Blood pressure (BP) is controlled primarily by Na and water balance because of the infinite gain property of the kidneys to rapidly eliminate excess fluid and salt.
Renal sodium handling is a sequential mechanism aimed to reasorb the most part of filtred sodium.
This handling occurs in different part of the tubule throuht different active and passive trasports.
We focoused on renal sodium handling beacause is well known that an increase in overall tubular sodium reabsorbtion leads to salt sensitive hypertension.
Up to fifty percent of patients with essential hypertension are salt-sensitive, as manifested by a rise in BP with salt loading.
S Exmple, In the proximal tubule The driving force is the Sodim-potassium ATPase wherease in the distal tubule in the sodium.cloride cotransport.(taget of diuretic)
Figure 2. Molecular Mechanisms Implicated in the Retention of Sodium and Loss of Potassium by the Kidneys in Primary Hypertension. Solid arrows indicate an increase or stimulation, and the broken arrow indicates inhibition. Numbers on the left denote the approximate percentage of reabsorption of filtered sodium in each nephronal segment during normal conditions. Several influences acting on the luminal sodium transporters and the basolateral sodium pump stimulate sodium retention and potassium loss. Promotion of sodium reabsorption by the activated epithelial sodium channel (ENaC) generates a more negative luminal membrane voltage (Vm) in the collecting duct that enhances potassium secretion through the luminal potassium channel and promotes kaliuresis. NHE-3 denotes sodium–hydrogen exchanger type 3, ACE angiotensin-converting enzyme, NKCC2 sodium–potassium2 chloride cotransporter, and NCC sodium–chloride cotransporter. PST 2238 (rostafuroxin) antagonizes the effect of digitalis-like factor on the sodium pump.
Schematic of the Brenner hypothesis depicting how a low nephron number can result in hypertension and glomerular damage. An important limitation of the hypothesis is that it ignores that alterations in filtered load will induce changes in neuro-humoral control of tubular reabsorption of sodium and so maintain extracellular fluid homeostasis. For arterial pressure to become elevated in the setting of nephron deficiency, chronic alterations in struc- ture and function of not only the glomerulus, but also the tubule, have to occur. ECF, extracellular fluid; SNGFR, single nephron glomerular filtration rate.
Characterization of pressure-natriuresis relationship. Assuming a linear relationship between systemic mean arterial pressure (MAP) and daily urinary sodium excretion (UNaV), the pressure-natriuresis relationship is drawn by linking two data points, (x1, y1), (x2, y2), ob- tained in the steady state under two different amounts of sodium intake, low and high, in each subject, where MAP and UNaV are plotted on the x and y axes, respectively. Using the extrapolated x-intercept (A) and the slope (B) of this line, UNaV can now be represented as a first-order function of MAP: UNaV = B ¥ (MAP - A). Rearrangement of this equation gives MAP = A + UNaV/B. Since UNaV is equal to the amount of sodium intake (QNa) in the steady state, MAP = A + 1/B ¥ QNa. This important relationship indicates that 1/B is the factor to convert the amount of sodium intake into blood pressure, and there- fore represents sodium sensitivity. We define 1/B as the sodium sensi- tivity index (SI): SI = 1/B. Reproduced with permission from Kimura and Brenner70
Fig 4
Features of the chronic pressure natriuresis relationship. Line-a corresponds to the steady state relationship between salt intake and BP for a salt resistant individual in which changes from low to high salt intake is not associated with a change in steady state BP (points 1 vs. 2). Acute salt sensitivity of BP (Acute-Reversible component of the model) corresponds with a reduced slope of this relationship (e.g. line-b), such that increases in salt intake leads to increases in steady state BP (points 1 vs. 3), and restoration of a low salt intake will return BP along line-b to the original level (point 1). Dahl-S rats exhibit acute salt sensitivity which appears to progressively worsen with salt exposure (Acute-Reversible component of the model, line c). The Progressive-Irreversible component of the model is represented by a progressive salt-induced rightward shift of the relationship along the x-axis to high BP levels (line d). The irreversible nature of the shift is associated with a shift in the baseline (from point 1 to 6), such that BP will remain elevated even following a return to low salt intake along line-d. The three component model is able to represent any salt-induced increase in BP (e.g. from the initial baseline, point 1, to a salt-induced increase in BP, point 3, 4, or 5) in terms of the initial slope and position of the relationship at baseline, combined with the independent effects of salt intake on the slope and position of the relationship.
Schematic drawing show- ing steady-state relations between arte- rial pressure and sodium excretion and sodium intake in various forms of hypertension. K^, glomerular capillary filtration coefficient; SHR, spontane- ously hypertensive rats; Goldblatt, one- kidney, one clip Goldblatt hypertensive rats.
To asses the salt sensitive hypertension, we use an Acute salt load test. For our study we enrolled 626 newly discovered and never treated hypertensive patients coming from the outpatient clinic of hypertension of the hospital.
The test consists of on an infusion of 2l of saline solution for 2 hours, after that we measured blood pressure and we collected plasma and urine samples.
This graph represents the individual blood pressure response to Na loading. Each line represents the individual blood pressure. Salt sensitive patients (red lines) respond to acute test with an increase of SBP, but in salt resistent patients (blu line) the blood pressure deacrease. This graph represents the pressure natriuresis mechanism. Salt sensivite patients need to increase their blood pressure to remove the same amount of sodium compared to salt resistent subjects.
OA genotype association study detected a strong association with variation in BP after acute sodium load with 8 genes (ADD1, NCX1, NEDD4L, PRKG1, MYO32, SIK1 and UMOD). In combined analyses, we found significant epistatic interactions between these SNPs. OA genotype association study detected a strong association with variation in BP after acute sodium load with 8 genes (ADD1, NCX1, NEDD4L, PRKG1, MYO, MYO32, SIK1 and UMOD). In combined analyses, we found significant epistatic interactions between these SNPs.
A genetic profile is a specific combination of variants in terms of SNPs or SNP interactions. Furthermore, we built a genetic profile able to identify the SS and SR hypertensive: those carrying the SS profile display changes in systolic BP of 10.4±1.25 vs 2.99±0.39 mmHg p<0.0001).
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