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The balance hypothesis of renin release
Medical Hypotheses(1997) 49, 421--423 © Pearson Professional Ltd 1997
The balance hypothesis of renin release PING-TIAN XIAO XiangYa Hospital, Hunen Medical University, Changsha 410008, People's Republic of China
There is much research on renin release, but there are still some controversies according to the literature (1). The factors that increase renin release include: (a) low sodium diet; however, it was also reported that a high sodium diet may also increase renin release (2); (b) stimulation of sympathetic nerves either electrically or by adrenaline, but it was also reported that renin release remains the same after renal denervation (1); (c) decrease in sodium ion concentration in the macula densa portion of the distal tubule (MDPT). But there was an opposite viewpoint (3,4); (d) decrease in blood pressure, water deprivation (5), increase in plasma colloid osmotic pressure, ligation of the ureter, electrical stimulation of the brain and a decrease in sodium concentration in the cerebrospinal fluid. The factors which decrease renin release are injection of A2 (angiotensin 2), A3 (angiotensin 3) and some anaesthetics. Perhaps the balance hypothesis of renin release adjustment can answer some of the above controversies. The negative feedback mechanism is the reason why the renal tubule returns to the cortex from the medulla and forms the juxtaglomerular apparature with the hypertrophic wall of its own (macula densa) and that of the afferent arteriole (AA). The renin is stored between the MDPT and the AA. The situation provides a balance, with MDPT and AA being the two sides of the balance. The juxtaglomerular apparatus (JGA) is like the fulcrum of the balance, and its state indicates the amount of renin release (see Fig. 1). The amount of renin release perhaps varies in response to RNC (RNC is the ratio of Na ÷ in AA to to Na ÷ in MDPT), RSF (RSF is the
I
I
I
I
I Na+ concentration I ,1Speed of blood
a'onoqa*ioI
Speed of fluid flow
t
Amount of renin
Pressure in AA
JGA
Pressure in MDPT
Fig. 1 Increased Na+ and speed of blood flow in the AA promote renin release, while increased pressure diminishes renin release. The opposite is true in the MDPT. The amount of renin release is related to the values of the ratios RNC, RP and RSF (see text).
ratio of speed of blood flow in AA to speed of fluid flow in MDPT) and RP (RP is the ratio of pressure in AA to pressure in MDPT).
The mechanism of renin release Effect of RNC on renin release
Renin is stored in juxtaglomerular cells which are separated from macula densa cells by a basement membrane. Figure 2 shows that Na ÷ in AA can result in increase in renin release and Na ÷ in MDPT inhibits
Date received 4 October 1995 Date accepted 24 October 1996
421
422
MEDICAL HYPOTHESES
Juxtaglomerular ceils
renin release increases. A high sodium diet may result in an increase of Na ÷ in AA, which increases renin release. An increase in renin release during a low sodium diet may relate to reduced blood volume and a decrease in sodium concentration in MDPT.
The pressure makes valve close and prevents renil release
Effect of RP on renin release Figures 1 and 2 show that the amount of renin release varies with RP. The pressure in MDPT is the driving force behind renin release. Renin release increases with a decrease in RP, and decreases when RP rises.
Speed of blood flow Fig. 2 Renin is stored in juxtaglomerular cells, which are separated from macula densa cells by the basement membrane. Renin can move into the AA, but hardly into the MDPT. Because of this characteristic constitution, the effects of renin release are different for each kind of tubule.
renin release. If there is a linkage between Na ÷ and renin, this will be possible. The amount of renin release varies with the RNC. The amount of renin release increases with an increase in RNC, and decreases with a decrease in RNC. As an increase in RNC may result from a decrease in Na ÷ in MDPT,
AA Pressure,[. Speedi'Na+~ ' MDPTPressure~ Speed.I,Na*/~
[Na+~Speed~ Pressuret, AA [Na+tSpeed4' Pressure~.MDPT
IRP* P.sF* ~c~l Fig. 3
M e , ,sF,
Negative feedback cycle of renin release adjustment.
Glomerular filtration t
Pr A2 Col Blo
distal tubule _': Aldosterone and t. A2 and A3'~
;_ antidiuretic
Isoprotere~ dilation of Low blood
J
Water de1
High-sodi Low-sodium met Fig. 4
Glomerular filtration¢-*Flow speed in renal tubule¢*Counter current muitiplierq
The mechanism of the negative feedback cycle of Fig. 3.
]
THEBALANCEHYPOTHESISOFRENINRELEASE RP decreases when the pressure in AA decreases as a result of low blood pressure, so that renin release increases. Renin release increases after ureteric ligation, because pressure in MDPT is increased, resulting in a decrease in RP. Effect on R S F on renin release
Renin is located between AA and MDPT, where speed of fluid flow affects renin release. The pressure on the JGA decreases when the speed of blood flow in AA increases. That causes renin release to rise. If the fluid lateral pressure on JGA increases when the speed of fluid flow in MDPT decreases, renin release increases. For example, renin release increases during low blood pressure or after ureteric ligation. From the above, it can be seen that renin release varies with RSF as well. Renin release increases when RSF increases. The speed of blood flow in AA relates to RV (RV is the ratio of calibre of AA to calibre of EA, where EA is efferent arteriole). Sympathetic nerves may affect RV (6), and the activity of cAMP changes the RSF, RP and RNC, and so changes the renin release. The effect of sympathetic nerves on renin release is indirect. The effect of sympathetic nerves on renin release can be replaced by other factors, so that renal denervation does not substantially change renin release. The increase in renin release during acute renal failure results from an
423 increase in RSF and decrease in sodium concentration in MDPT. The phenomenon that renin release is higher during the day than at night may relate to the variation of RSF.
Negative feedback cycle of renin release adjustment and its mechanism Renin release is adjusted by the changes of RNC, RSF and RP. Renin produces changes of RNC, RP and RSF resulting from the effects of renin on blood pressure, blood sodium ion concentration, blood volume, sympathetic nerves, etc. They form a negative feedback cycle (see Fig. 3), whose mechanism is shown in Fig. 4.
References 1. Din Bau-chun.Renin-angiotensinsystem. Prog Phys Sci 1979; 10(4): 318. 2. Hunan Medical College: Physiology,1st edn. People's Health Publishing House, 1979:293. 3. VanderA J. Controlof renin secretion in the anesthetized dog. Am J Physiol 1964;207: 537. 4. ThurauK. Renalhemodynamics.Am J Med 1964;36: 698. 5. Carvalno J S. The effect of water deprivation on the osmotic release of renin. KidneyInt 1982;22(4): 344-347. 6. Jior Misumi et al. Regulationof kaUikrein and renin release by the isolated perfusedkidney. KidneyInt 1983;24(1): 58--65.
The balance hypothesis of renin release PING-TIAN XIAO XiangYa Hospital, Hunen Medical University, Changsha 410008, People's Republic of China
There is much research on renin release, but there are still some controversies according to the literature (1). The factors that increase renin release include: (a) low sodium diet; however, it was also reported that a high sodium diet may also increase renin release (2); (b) stimulation of sympathetic nerves either electrically or by adrenaline, but it was also reported that renin release remains the same after renal denervation (1); (c) decrease in sodium ion concentration in the macula densa portion of the distal tubule (MDPT). But there was an opposite viewpoint (3,4); (d) decrease in blood pressure, water deprivation (5), increase in plasma colloid osmotic pressure, ligation of the ureter, electrical stimulation of the brain and a decrease in sodium concentration in the cerebrospinal fluid. The factors which decrease renin release are injection of A2 (angiotensin 2), A3 (angiotensin 3) and some anaesthetics. Perhaps the balance hypothesis of renin release adjustment can answer some of the above controversies. The negative feedback mechanism is the reason why the renal tubule returns to the cortex from the medulla and forms the juxtaglomerular apparature with the hypertrophic wall of its own (macula densa) and that of the afferent arteriole (AA). The renin is stored between the MDPT and the AA. The situation provides a balance, with MDPT and AA being the two sides of the balance. The juxtaglomerular apparatus (JGA) is like the fulcrum of the balance, and its state indicates the amount of renin release (see Fig. 1). The amount of renin release perhaps varies in response to RNC (RNC is the ratio of Na ÷ in AA to to Na ÷ in MDPT), RSF (RSF is the
I
I
I
I
I Na+ concentration I ,1Speed of blood
a'onoqa*ioI
Speed of fluid flow
t
Amount of renin
Pressure in AA
JGA
Pressure in MDPT
Fig. 1 Increased Na+ and speed of blood flow in the AA promote renin release, while increased pressure diminishes renin release. The opposite is true in the MDPT. The amount of renin release is related to the values of the ratios RNC, RP and RSF (see text).
ratio of speed of blood flow in AA to speed of fluid flow in MDPT) and RP (RP is the ratio of pressure in AA to pressure in MDPT).
The mechanism of renin release Effect of RNC on renin release
Renin is stored in juxtaglomerular cells which are separated from macula densa cells by a basement membrane. Figure 2 shows that Na ÷ in AA can result in increase in renin release and Na ÷ in MDPT inhibits
Date received 4 October 1995 Date accepted 24 October 1996
421
422
MEDICAL HYPOTHESES
Juxtaglomerular ceils
renin release increases. A high sodium diet may result in an increase of Na ÷ in AA, which increases renin release. An increase in renin release during a low sodium diet may relate to reduced blood volume and a decrease in sodium concentration in MDPT.
The pressure makes valve close and prevents renil release
Effect of RP on renin release Figures 1 and 2 show that the amount of renin release varies with RP. The pressure in MDPT is the driving force behind renin release. Renin release increases with a decrease in RP, and decreases when RP rises.
Speed of blood flow Fig. 2 Renin is stored in juxtaglomerular cells, which are separated from macula densa cells by the basement membrane. Renin can move into the AA, but hardly into the MDPT. Because of this characteristic constitution, the effects of renin release are different for each kind of tubule.
renin release. If there is a linkage between Na ÷ and renin, this will be possible. The amount of renin release varies with the RNC. The amount of renin release increases with an increase in RNC, and decreases with a decrease in RNC. As an increase in RNC may result from a decrease in Na ÷ in MDPT,
AA Pressure,[. Speedi'Na+~ ' MDPTPressure~ Speed.I,Na*/~
[Na+~Speed~ Pressuret, AA [Na+tSpeed4' Pressure~.MDPT
IRP* P.sF* ~c~l Fig. 3
M e , ,sF,
Negative feedback cycle of renin release adjustment.
Glomerular filtration t
Pr A2 Col Blo
distal tubule _': Aldosterone and t. A2 and A3'~
;_ antidiuretic
Isoprotere~ dilation of Low blood
J
Water de1
High-sodi Low-sodium met Fig. 4
Glomerular filtration¢-*Flow speed in renal tubule¢*Counter current muitiplierq
The mechanism of the negative feedback cycle of Fig. 3.
]
THEBALANCEHYPOTHESISOFRENINRELEASE RP decreases when the pressure in AA decreases as a result of low blood pressure, so that renin release increases. Renin release increases after ureteric ligation, because pressure in MDPT is increased, resulting in a decrease in RP. Effect on R S F on renin release
Renin is located between AA and MDPT, where speed of fluid flow affects renin release. The pressure on the JGA decreases when the speed of blood flow in AA increases. That causes renin release to rise. If the fluid lateral pressure on JGA increases when the speed of fluid flow in MDPT decreases, renin release increases. For example, renin release increases during low blood pressure or after ureteric ligation. From the above, it can be seen that renin release varies with RSF as well. Renin release increases when RSF increases. The speed of blood flow in AA relates to RV (RV is the ratio of calibre of AA to calibre of EA, where EA is efferent arteriole). Sympathetic nerves may affect RV (6), and the activity of cAMP changes the RSF, RP and RNC, and so changes the renin release. The effect of sympathetic nerves on renin release is indirect. The effect of sympathetic nerves on renin release can be replaced by other factors, so that renal denervation does not substantially change renin release. The increase in renin release during acute renal failure results from an
423 increase in RSF and decrease in sodium concentration in MDPT. The phenomenon that renin release is higher during the day than at night may relate to the variation of RSF.
Negative feedback cycle of renin release adjustment and its mechanism Renin release is adjusted by the changes of RNC, RSF and RP. Renin produces changes of RNC, RP and RSF resulting from the effects of renin on blood pressure, blood sodium ion concentration, blood volume, sympathetic nerves, etc. They form a negative feedback cycle (see Fig. 3), whose mechanism is shown in Fig. 4.
References 1. Din Bau-chun.Renin-angiotensinsystem. Prog Phys Sci 1979; 10(4): 318. 2. Hunan Medical College: Physiology,1st edn. People's Health Publishing House, 1979:293. 3. VanderA J. Controlof renin secretion in the anesthetized dog. Am J Physiol 1964;207: 537. 4. ThurauK. Renalhemodynamics.Am J Med 1964;36: 698. 5. Carvalno J S. The effect of water deprivation on the osmotic release of renin. KidneyInt 1982;22(4): 344-347. 6. Jior Misumi et al. Regulationof kaUikrein and renin release by the isolated perfusedkidney. KidneyInt 1983;24(1): 58--65.