Adenosine A2 Receptor-Mediated Regulation of Renal Hemodynamics and Glomerular Filtration Rate Is Abolished in Diabetes

The effects of l-epinephrine, l-norepinephrine, phenylephrine, methoxamine, metaraminol and mephentermine on renal hemodynamics were studied in six groups of dogs. Although comparable rises in blood pressure were obtained, there were marked differences in the effects on renal hemodynamics. While infusion of mephentermine led to only slight reductions in glomerular filtration rate and renal blood flow, and only a slight increase in renal vascular resistance, methoxamine produced a marked fall in flow and a marked increase in resistance. The other agents tested had effects which were intermediate between these two. The effects of these same drugs on renal hemodynamics were also compared in dogs made hypotensive by bleeding. While blood pressure increased significantly in all groups, glomerular filtration rate and renal blood flow increased significantly only during infusion of mephentermine, metaraminol and phenylephrine. Since assays relative to the inherent vasodilator properties of these agents revealed epinephrine to be the only agent with marked activity, it seems unlikely that the observed effects were due to this factor. It is concluded that the observed changes were due to a greater reactivity of renal vascular vasoconstrictor adrenergic receptors with certain sympathicomimetic drugs than those of the vasculature in general.

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Impaired renal hemodynamics and glomerular hyperfiltration contribute to hypertension-induced renal injury

AJP Renal Physiology ◽

10.1152/ajprenal.00239.2020 ◽

2020 ◽

Vol 319 (4) ◽

pp. F624-F635 ◽

Cited By ~ 2

Author(s):

Letao Fan ◽

Wenjun Gao ◽

Bond V. Nguyen ◽

Joshua R. Jefferson ◽

Yedan Liu ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Capillary Pressure ◽

Renal Injury ◽

Filtration Rate ◽

Time Course ◽

Renal Hemodynamics ◽

Myogenic Response ◽

Glomerular Capillary ◽

Glomerular Capillary Pressure

Recently, we reported a mutation in γ-adducin (ADD3) was associated with an impaired myogenic response of the afferent arteriole and hypertension-induced chronic kidney disease (CKD) in fawn hooded hypertensive (FHH) rats. However, the mechanisms by which altered renal blood flow (RBF) autoregulation promotes hypertension-induced renal injury remain to be determined. The present study compared the time course of changes in renal hemodynamics and the progression of CKD during the development of DOCA-salt hypertension in FHH 1BN congenic rats [wild-type (WT)] with an intact myogenic response versus FHH 1BN Add3KO ( Add3KO) rats, which have impaired myogenic response. RBF was well autoregulated in WT rats but not in Add3KO rats. Glomerular capillary pressure rose by 6 versus 14 mmHg in WT versus Add3KO rats when blood pressure increased from 100 to 150 mmHg. After 1 wk of hypertension, glomerular filtration rate increased by 38% and glomerular nephrin expression decreased by 20% in Add3KO rats. Neither were altered in WT rats. Proteinuria doubled in WT rats versus a sixfold increase in Add3KO rats. The degree of renal injury was greater in Add3KO than WT rats after 3 wk of hypertension. RBF, glomerular filtration rate, and glomerular capillary pressure were lower by 20%, 28%, and 19% in Add3KO rats than in WT rats, which was associated with glomerular matrix expansion and loss of capillary filtration area. The results indicated that impaired RBF autoregulation and eutrophic remodeling of preglomerular arterioles increase the transmission of pressure to glomeruli, which induces podocyte loss and accelerates the progression of CKD in hypertensive Add3KO rats.

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A Pilot Study to Evaluate Renal Hemodynamics in Cirrhosis by Simultaneous Glomerular Filtration Rate, Renal Plasma Flow, Renal Resistive Indices and Biomarkers Measurements

American Journal of Nephrology ◽

10.1159/000363584 ◽

2014 ◽

Vol 39 (6) ◽

pp. 543-552 ◽

Cited By ~ 17

Author(s):

Ayse L. Mindikoglu ◽

Thomas C. Dowling ◽

Jade J. Wong-You-Cheong ◽

Robert H. Christenson ◽

Laurence S. Magder ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

Pilot Study ◽

Glomerular Filtration ◽

Plasma Flow ◽

Filtration Rate ◽

Renal Plasma Flow ◽

Renal Hemodynamics

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Sex differences in renal hemodynamics in rats

AJP Renal Physiology ◽

10.1152/ajprenal.1988.254.2.f223 ◽

1988 ◽

Vol 254 (2) ◽

pp. F223-F231 ◽

Cited By ~ 24

Author(s):

K. Munger ◽

C. Baylis

Keyword(s):

Sex Differences ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Plasma Flow ◽

Filtration Rate ◽

Renal Hemodynamics ◽

Female Rats ◽

Male And Female ◽

Cyclooxygenase Inhibition ◽

Male And Female Rats

These studies were designed to investigate sex differences in renal hemodynamics under control conditions and in response to two different cyclooxygenase inhibitors. Studies were performed under anesthesia in males, females, and ovariectomized (OVX) rats and in separate groups of conscious, chronically catheterized male and female rats of a different strain. In the control periods, before cyclooxygenase inhibition, the male kidney was vasodilated relative to the female. Because male and female rats have the same number of glomeruli per kidney, the total vascular resistance per glomerulus is substantially greater in females than males. Cyclooxygenase inhibition in the anesthetized intact female rat produced significant increases in single-nephron glomerular filtration rate, glomerular plasma flow rate, glomerular filtration rate, and renal plasma flow, whereas afferent and efferent arteriolar resistances and renal vascular resistance fell. In contrast, anesthetized male and OVX female rats showed no renal hemodynamic response to cyclooxygenase inhibition. In the absence of anesthesia and recent surgery, intact awake female rats responded similarly to conscious male rats in that neither showed any response to cyclooxygenase inhibition. These data suggest a functional sex difference in both baseline renal hemodynamics and the renal response to cyclooxygenase inhibition, the latter unveiled by surgical stress.

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Hyperfiltration in ubiquitin C-terminal hydrolase L1-deleted mice

Clinical Science ◽

10.1042/cs20180085 ◽

2018 ◽

Vol 132 (13) ◽

pp. 1453-1470 ◽

Cited By ~ 2

Author(s):

Naomi C. Boisvert ◽

Chet E. Holterman ◽

Jean-François Thibodeau ◽

Rania Nasrallah ◽

Eldjonai Kamto ◽

...

Keyword(s):

Nitric Oxide ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Vascular Reactivity ◽

Renal Hemodynamics ◽

Cyclooxygenase 2 ◽

Glomerular Hyperfiltration ◽

Angiotensin Converting Enzyme Inhibition ◽

Renal Nerve

Neuronal ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that maintains intracellular ubiquitin pools and promotes axonal transport. Uchl1 deletion in mice leads to progressive axonal degeneration, affecting the dorsal root ganglion that harbors axons emanating to the kidney. Innervation is a crucial regulator of renal hemodynamics, though the contribution of neuronal UCHL1 to this is unclear. Immunofluorescence revealed significant neuronal UCHL1 expression in mouse kidney, including periglomerular axons. Glomerular filtration rate trended higher in 6-week-old Uchl1-/- mice, and by 12 weeks of age, these displayed significant glomerular hyperfiltration, coincident with the onset of neurodegeneration. Angiotensin converting enzyme inhibition had no effect on glomerular filtration rate of Uchl1-/- mice indicating that the renin–angiotensin system does not contribute to the observed hyperfiltration. DCE-MRI revealed increased cortical renal blood flow in Uchl1-/- mice, suggesting that hyperfiltration results from afferent arteriole dilation. Nonetheless, hyperglycemia, cyclooxygenase-2, and nitric oxide synthases were ruled out as sources of hyperfiltration in Uchl1-/- mice as glomerular filtration rate remained unchanged following insulin treatment, and cyclooxygenase-2 and nitric oxide synthase inhibition. Finally, renal nerve dysfunction in Uchl1-/- mice is suggested given increased renal nerve arborization, decreased urinary norepinephrine, and impaired vascular reactivity. Uchl1-deleted mice demonstrate glomerular hyperfiltration associated with renal neuronal dysfunction, suggesting that neuronal UCHL1 plays a crucial role in regulating renal hemodynamics.

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Renal hemodynamics in conscious rats: effects of anesthesia, surgery, and recovery

AJP Renal Physiology ◽

10.1152/ajprenal.1983.245.1.f67 ◽

1983 ◽

Vol 245 (1) ◽

pp. F67-F74 ◽

Cited By ~ 17

Author(s):

L. A. Walker ◽

M. Buscemi-Bergin ◽

M. Gellai

Keyword(s):

Blood Flow ◽

Renal Function ◽

Glomerular Filtration Rate ◽

Arterial Pressure ◽

Glomerular Filtration ◽

Renal Blood Flow ◽

Filtration Rate ◽

Severe Depression ◽

Renal Hemodynamics ◽

Ether Anesthesia

The influence of barbiturate anesthesia and minor surgical incisions on renal function was assessed in trained, chronically catheterized rats. In addition, renal hemodynamic changes during recovery from ether anesthesia and surgery were examined. Administration of pentobarbital in the chronic animals was associated with a marked reduction in arterial pressure (108 +/- 5 vs. 85 +/- 2 mmHg, P less than 0.01), renal blood flow (8.28 +/- 0.50 vs. 6.20 +/- 0.53 ml X min-1 X 100 g body wt-1, P less than 0.01), and glomerular filtration rate (1.30 +/- 0.10 vs. 0.97 +/- 0.11 ml X min-1 X 100 g body wt-1, P less than 0.01). Responses to Inactin were essentially identical. Small skin incisions during barbiturate anesthesia caused blood pressure to rise, but did not significantly change renal function parameters from already reduced values. In rats studied 2 h after ether anesthesia and surgical placement of catheters, arterial pressure was elevated compared with the same rats studied 4-7 days later (127 +/- 3 vs. 109 +/- 3 mmHg, P less than 0.005). Renal blood flow (5.80 +/- 0.37 vs. 8.90 +/- 0.93 ml X min-1 X 100 g body wt-1, P less than 0.01) and glomerular filtration rate (0.81 +/- 0.07 vs. 1.05 +/- 0.08 ml X min-1 X 100 g body wt-1, P less than 0.001) were markedly depressed during the recovery from surgery. It is concluded that barbiturate anesthesia depresses renal function in rats. This impairment should be considered when interpreting experiments that must be performed under anesthesia. In addition, the "conscious" preparation commonly used for renal studies in rats, i.e., one involving experimentation 2-3 h after ether anesthesia and surgery, is associated with a severe depression of renal hemodynamics.

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