Relative roles of nitric oxide, prostanoids and angiotensin II in the regulation of canine glomerular hemodynamics. A micropuncture study.

Glomerular hemodynamics are controlled by a variety of physical, nervous and hormonal factors including the potent vasoconstrictors, angiotensin (ANG) II and endothelin-1 (ET-1), and the vasodilator prostanoids (prostaglandin = PG) and nitric oxide (NO). Since no micropuncture data on the canine kidney exist with respect to the relative roles of the endogenous vasoactive hormones/autacoids NO, PG and ANG II in modulating glomerular hemodynamics, in the present study using the micropuncture technique in anesthetized dogs on a normal salt intake, we investigated the relative effects of these hormones/autacoids by means of the L-arginine analog, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME), a competitive NO synthase (NOS) inhibitor, the cyclooxygenase inhibitor indomethacin (INDO), and the AT(1) receptor blocker EXP 3174. An intrarenal arterial (i.

Genetic inactivation of the B2 receptor in mice worsens two-kidney, one-clip hypertension: role of NO and the AT2 receptor.

Objective: Previous studies have suggested that activation of angiotensin II (ANG II) type 2 (AT2) receptors results in nitric oxide (NO) release via activation of endothelial bradykinin B2 (B2R) receptors. The present study was performed to examine the interplay of AT2 and B2R in the development and maintenance of two-kidney, one-clip (2K1C) Goldblatt hypertension.

Methods: B2R knockout (B2R-/-) mice and their wild-type controls (B2R+/+) underwent clipping of the right renal artery and were infused with either saline (SAL) or PD 123319, an AT2 receptor antagonist (PD), via an osmotic pump implanted intraperitoneally.

Essential role of AT1A receptor in the development of 2K1C hypertension.

The aims of this study were to delineate the relative contribution of angiotensin II (ANG II) subtype 1A (AT1A) and 1B (AT1B) receptors to the development of two-kidney, one-clip (2K1C) Goldblatt hypertension in mice, to examine if increased nitric oxide synthase (NOS) activity counteracts the vasoconstrictor influences of ANG II in 2K1C hypertensive mice, and to determine the role of ANG II type 2 (AT2) receptors in 2K1C hypertension in mice. AT(1A) ANG II receptor knockout (AT1A-/-) and wild-type (AT1A+/+) mice underwent clipping of the right renal artery. Systolic blood pressure (SBP) was significantly lower in AT1A-/- compared with AT1A+/+ mice, and neither clip placement nor AT2 receptor blockade with PD 123319 (PD) altered SBP in AT1A-/- mice.

Effect of intrarenal infusion of angiotensin-(1-7) in the dog.

Angiotensin-(1-7), (Ang-(1-7)), a metabolite of Ang II and /or Ang I, was infused into the renal artery (i.r.a) of anesthetized dogs in order to demonstrate its possible direct renal action.

Glomerular haemodynamics during renal artery clamping and haemorrhage in the dog.

The influence of gradual decline in renal perfusion pressure (RPP) due either to renal artery clamping (C) or to haemorrhagic hypotension (HH) was studied using micropuncture techniques in anaesthetized dogs. The decrease in renal blood flow (RBF) was more profound and set in earlier during HH than during C, where perfect autoregulation was observed down to a mean arterial blood pressure of 85 mmHg. Glomerular filtration rate (GFR) was also only slightly decreased during C, with no change in filtration fraction (FF); again, a much greater decrease in GFR with an increase in FF was seen in HH.

Comparative effects of the angiotensin II receptor blocker EXP 3174 and of the angiotensin-converting enzyme inhibitor captopril on renal glomerular hemodynamics in the dog.

The effects on glomerular hemodynamics of angiotensin-converting enzyme (ACE) inhibition with captopril and of angiotensin II receptor blockade with EXP 3174, an active metabolite of losartan, either alone or in combination, were compared in anesthetized dogs. Administration of EXP 3174 intrarenally led to an increase in renal blood flow by +14% and in glomerular filtration rate by +7%, thus decreasing the filtration fraction by -5%. Similar changes were observed at the single-nephron level.

Effect of PD 123319, an AT-2 antagonist, on renal function of the anesthetized dog: comparison with EXP 3174, an AT-1 blocker.

In anaesthetized dogs fed a diet delivering 3.5 mmol NaCl/kg/day, PD 123319 - an angiotensin (AT) II (Ang II) antagonist preferentially bound to AT-2 receptors - was infused into the renal artery for 20 min at 10 microg/kg/min, the lowest effective dose (group 1 dogs). In group 2 dogs, EXP 3174 (30 microg/kg/min) - an AT-1 blocker - was coinfused while, in group 3, EXP 3174 was infused alone.

Action of endothelin-1 on glomerular haemodynamics in the dog: lack of direct effects on glomerular ultrafiltration coefficient.

1. Although numerous studies have demonstrated the potent vasoconstrictor effect of endothelin-1 on the renal vasculature, it is difficult to differentiate in vivo between indirect and direct actions of endothelin. 2.

The effect of kinin and prostaglandin inhibitors on the renal response to angiotensin-converting enzyme inhibition: a micropuncture study in the dog.

It has been suggested that angiotensin-converting enzyme (ACE) inhibition is accompanied by enhanced bradykinin and prostaglandin activities, which may contribute to the renal haemodynamic actions of ACE inhibitors. Therefore we investigated renal function by clearance and micropuncture techniques in dogs maintained either on normal or low-salt diet before and after ACE inhibition with an i.v.

The cause of a depressed glomerular filtration rate after an ischaemic insult: whole kidney and superficial nephron study in the dog.

Twenty-four hours after 90 min clamping of the left renal artery in dogs, the glomerular filtration rate (GFR) was decreased in the whole kidney (0.34 ml.min-1g KW-1 [KW = Kidney weight] vs 0.

The effect of two different calcium antagonists on the glomerular haemodynamics in the dog.

Kidney function of beagles fed a constant amount of food containing 3 mmol sodium.kgbodywt-1.day-1, and anaesthetized with pentobarbitone was investigated by clearance and micropuncture techniques during an intrarenal infusion of saline or the calcium antagonists verapamil (VER, 4 micrograms.

A possible role for leukotrienes in the regulation of glomerular haemodynamics in the dog.

In anaesthetized beagles, saralasin, phentolamine, 1-penicillamine-2-O-methyl-tyrosine-8-arginine-vasopressin and SCH 23390, a DA1 antagonist, were infused into the left renal artery (i.r.a.

Protein aggregates in extracorporally perfused rabbit kidneys.

Eighteen rabbit kidneys were perfused ex vivo for 1 h with allogeneic blood, and in 16 a solution of xenogeneic aggregate-free, aggregated or antibody-complexed protein was added to the perfusate 5 min after the start (human immunoglobulins or serum albumin, partly cationized, were used). The kidneys were examined by light and electron microscopy and the human and rabbit immunoglobulin (or albumin) precipitates were detected by direct immunofluorescence and ultrastructural immunohistochemistry. In 13 kidneys the perfusion produced small segmental glomerular endocapillary aggregates of platelets, leukocytes, and granular precipitates reactive with both anti-rabbit and anti-human antibodies.

Hemodynamics of the recently opened glomeruli. Micropuncture study in 22- to 26-day-old puppies.

In 22- to 26-day-old beagle puppies, just after superficial nephrons have begun to function, the single nephron glomerular filtration rate is extremely low (6.7 nl.min-1) approximating a tenth of the adult value (57 nl.

Prostacyclin prevents hyperacute xenogenous rejection of the kidney.

The rabbit kidney, perfused under a constant pressure from the canine femoral artery is rejected (i.e. blood flow arrests) within several minutes.

Angiotensin II: preferential efferent constriction?

In dogs with maximal subpression of endogenous angiotensin II (AII) production due to a high-salt diet and converting enzyme inhibition (CEI, SQ 14,225, 15 micrograms X kg-1 X min-1 i.v.), infusion of a subpressor dose of angiotensin II (1 ng X kg-1 X min-1) did not change contralateral kidney function.

Kidney function during decreased perfusion pressure due to aortic clamping and hemorrhagic hypotension: a single nephron study in dog kidney.

Whole kidney and single nephron function was compared in dogs during a stepwise lowering of renal perfusion pressure (PP) induced by aortic clamping (C) or hemorrhagic hypotension (HH). In C, renal vascular resistance (RVR) decreased with decreasing PP, the decrease being due to a drop in afferent resistance (RA) only. HH was associated with a rise in RVR due in the first phase mainly to an increase in RE, later to both RA and RE.

Comparison of directly measured and calculated glomerular capillary pressure in the dog kidney at varying perfusion pressure.

To gain access to glomeruli of the dog kidney, an approximately 0.3 mm thick superficial tissue layer was cut off from the convexity of the kidney. The surface was superfused with warm Ringer's.

Autoregulation of superficial nephron function in the alloperfused dog kidney.

Isolated dog kidneys were each pump-perfused by another dog during 4 experimental periods at perfusion pressures (PP) of 21, 17, 13, and 8 kPa, resp. (i.e.

Renal blood flow distribution at varying perfusion pressure in the alloperfused dog kidney.

Tissue blood flow (TBF), its percent distribution and glomerular blood flow (GBF) were measured using labelled microspheres 15 micrometer in diameter (M) and chicken red blood cells (CRBC) at perfusion pressures (PP) of 17.3, 12.8 and 8.

Autoregulation of renal blood flow in the rat.

Renal blood flow was measured in rats anaesthetized with pentobarbital sodium by employing the PAH clearance method and the 133Xe washout technique. Both methods were in good agreement. In 17 rats a 25% decrement of blood pressure was attained through haemorrhage: RBF measured by PAH clearance declined by 3%, according to 133Xe washout by 2.