Biomaterial Database

Renal interstitial atp responses to changes in arterial pressure during alterations in tubuloglomerular feedback activity. 2001

A Nishiyama, and D S Majid, and M Walker, and A Miyatake, and L G Navar

Department of Physiology, Tulane University Health Sciences Center, New Orleans, LA, USA. anishiy@tulane.edu

We recently demonstrated a direct relationship between autoregulation-related changes in renal vascular resistance (RVR) and renal interstitial ATP concentrations. To assess the possible role for extracellular ATP in the regulation of tubuloglomerular feedback (TGF)-mediated autoregulatory adjustments in RVR, renal interstitial ATP concentrations were measured with microdialysis probes in anesthetized dogs at different renal arterial pressures (RAPs) within the autoregulatory range during augmented and diminished activity of the TGF mechanism. Stepwise reductions in RAP from ambient pressure (129+/-3 mm Hg) to 102+/-2 mm Hg (step 1) and 75+/-1 mm Hg (step 2) resulted in significant decreases in ATP concentrations from 9.0+/-0.8 to 6.3+/-0.6 nmol/L in step 1 and to 4.2+/-0.5 nmol/L in step 2. Changes in RVR were highly correlated with changes in ATP concentrations (r=0.86, P<0.001, n=12). Acetazolamide (100 microgram. kg(-1). min(-1), n=6), which increases solute delivery to the macula densa, thus augmenting TGF activity, significantly decreased renal blood flow (RBF) by -16+/-2% and glomerular filtration rate (GFR) by -22+/-4% and increased ATP concentrations from 8.4+/-0.7 to 15.5+/-1.4 nmol/L. Although basal RBF and GFR levels were reduced by the acetazolamide infusion, autoregulation efficiency was maintained, and interstitial ATP concentrations were significantly decreased in response to reductions in RAP by -36+/-4% in step 1 and by -54+/-2% in step 2. The relationship between changes in RVR and interstitial ATP concentrations was preserved during acetazolamide treatment (r=0.80, P<0.01). Inhibition of the TGF mechanism by furosemide significantly increased RBF by 33+/-6% and GFR by 13+/-2% and decreased ATP concentrations from 8.9+/-1.4 to 5.0+/-0.8 nmol/L (n=6). Furosemide caused marked impairment of RBF and GFR autoregulatory efficiency (by -14+/-3% and -11+/-3% in step 1 and by -26+/-2% and -18+/-4% in step 2, respectively). In the furosemide-treated kidneys, interstitial ATP levels remained low and were not altered during reductions in RAP (4.7+/-0.7 nmol/L in step 1 and 4.7+/-0.8 nmol/L in step 2), and changes in RVR did not exhibit a correlation with changes in ATP concentrations (r=0.22, P=0.30). These data support the hypothesis that extracellular ATP contributes to autoregulatory adjustments in RVR that are mediated by changes in activity of the TGF mechanism.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D007678	Kidney Glomerulus	A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.	Glomerulus, Kidney
D012039	Regional Blood Flow	The flow of BLOOD through or around an organ or region of the body.	Blood Flow, Regional,Blood Flows, Regional,Flow, Regional Blood,Flows, Regional Blood,Regional Blood Flows
D012077	Renal Artery	A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters.	Arteries, Renal,Artery, Renal,Renal Arteries
D001794	Blood Pressure	PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.	Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002257	Carbonic Anhydrase Inhibitors	A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES.	Carbonate Dehydratase Inhibitor,Carbonate Dehydratase Inhibitors,Carbonic Anhydrase Inhibitor,Carboxyanhydrase Inhibitor,Carboxyanhydrase Inhibitors,Anhydrase Inhibitor, Carbonic,Dehydratase Inhibitor, Carbonate,Inhibitor, Carbonate Dehydratase,Inhibitor, Carbonic Anhydrase,Inhibitor, Carboxyanhydrase,Inhibitors, Carbonate Dehydratase,Inhibitors, Carbonic Anhydrase,Inhibitors, Carboxyanhydrase
D004232	Diuretics	Agents that promote the excretion of urine through their effects on kidney function.	Diuretic,Diuretic Effect,Diuretic Effects,Effect, Diuretic,Effects, Diuretic
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D005110	Extracellular Space	Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall.	Intercellular Space,Extracellular Spaces,Intercellular Spaces,Space, Extracellular,Space, Intercellular,Spaces, Extracellular,Spaces, Intercellular
D005246	Feedback	A mechanism of communication within a system in that the input signal generates an output response which returns to influence the continued activity or productivity of that system.	Feedbacks