TY - JOUR
T1 - Coupling-induced complexity in nephron models of renal blood flow regulation
AU - Laugesen, Jakob L
AU - Sosnovtseva, Olga
AU - Mosekilde, Erik
AU - Holstein-Rathlou, Niels-Henrik
AU - Marsh, Donald J
N1 - Keywords: Animals; Arterioles; Blood Flow Velocity; Blood Pressure; Disease Models, Animal; Feedback; Homeostasis; Hypertension; Kidney Glomerulus; Kidney Tubules; Membrane Potentials; Models, Biological; Nephrons; Oscillometry; Rats; Renal Circulation
PY - 2010/4
Y1 - 2010/4
N2 - Tubular pressure and nephron blood flow time series display two interacting oscillations in rats with normal blood pressure. Tubuloglomerular feedback (TGF) senses NaCl concentration in tubular fluid at the macula densa, adjusts vascular resistance of the nephron's afferent arteriole, and generates the slower, larger-amplitude oscillations (0.02- 0.04 Hz). The faster smaller oscillations (0.1- 0.2 Hz) result from spontaneous contractions of vascular smooth muscle triggered by cyclic variations in membrane electrical potential. The two mechanisms interact in each nephron and combine to act as a high-pass filter, adjusting diameter of the afferent arteriole to limit changes of glomerular pressure caused by fluctuations of blood pressure. The oscillations become irregular in animals with chronic high blood pressure. TGF feedback gain is increased in hypertensive rats, leading to a stronger interaction between the two mechanisms. With a mathematical model that simulates tubular and arteriolar dynamics, we tested whether an increase in the interaction between TGF and the myogenic mechanism can cause the transition from periodic to irregular dynamics. A one-dimensional bifurcation analysis, using the coefficient that couples TGF and the myogenic mechanism as a bifurcation parameter, shows some regions with chaotic dynamics. With two nephrons coupled electrotonically, the chaotic regions become larger. The results support the hypothesis that increased oscillator interactions contribute to the transition to irregular fluctuations, especially when neighboring nephrons are coupled, which is the case in vivo.
AB - Tubular pressure and nephron blood flow time series display two interacting oscillations in rats with normal blood pressure. Tubuloglomerular feedback (TGF) senses NaCl concentration in tubular fluid at the macula densa, adjusts vascular resistance of the nephron's afferent arteriole, and generates the slower, larger-amplitude oscillations (0.02- 0.04 Hz). The faster smaller oscillations (0.1- 0.2 Hz) result from spontaneous contractions of vascular smooth muscle triggered by cyclic variations in membrane electrical potential. The two mechanisms interact in each nephron and combine to act as a high-pass filter, adjusting diameter of the afferent arteriole to limit changes of glomerular pressure caused by fluctuations of blood pressure. The oscillations become irregular in animals with chronic high blood pressure. TGF feedback gain is increased in hypertensive rats, leading to a stronger interaction between the two mechanisms. With a mathematical model that simulates tubular and arteriolar dynamics, we tested whether an increase in the interaction between TGF and the myogenic mechanism can cause the transition from periodic to irregular dynamics. A one-dimensional bifurcation analysis, using the coefficient that couples TGF and the myogenic mechanism as a bifurcation parameter, shows some regions with chaotic dynamics. With two nephrons coupled electrotonically, the chaotic regions become larger. The results support the hypothesis that increased oscillator interactions contribute to the transition to irregular fluctuations, especially when neighboring nephrons are coupled, which is the case in vivo.
U2 - 10.1152/ajpregu.00714.2009
DO - 10.1152/ajpregu.00714.2009
M3 - Journal article
C2 - 20147606
SN - 0363-6119
VL - 298
SP - R997-R1006
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 4
ER -