Coupling-induced complexity in nephron models of renal blood flow regulation.
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.
Department of Molecular Pharmacology, Brown University, Biomedical Center B-3, Providence, RI 02912, USA.
Jakob L
JL
Laugesen
Olga V
OV
Sosnovtseva
Erik
E
Mosekilde
Niels-Henrik
NH
Holstein-Rathlou
Donald J
DJ
Marsh
D000818:Animals; D001160:Arterioles / Q000502:physiology; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000502:physiology*; D004195:Disease Models, Animal; D005246:Feedback; D006706:Homeostasis / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000502:physiology; D007684:Kidney Tubules / Q000098:blood supply / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology*; D008954:Models, Biological; D009399:Nephrons / Q000502:physiology*; D009991:Oscillometry; D051381:Rats; D012079:Renal Circulation / Q000502:physiology*