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

Heller, J; Kramer, Herbert J.; Horáček, Vladislav

doi:10.1007/bf00374527

Cited by 19 publications

(10 citation statements)

References 20 publications

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“…Renal arteriolar resistance (R) values, effective filtration pressure (EFP) and glomerular capillary ultrafiltration coefficient (K f ) were calculated as described previously [21,22]. EFP is proportional to the imbalance between the transmural hydrostatic and colloid osmotic pressures.…”

Section: Experimental Techniquesmentioning

confidence: 99%

Relative Roles of Nitric Oxide, Prostanoids and Angiotensin II in the Regulation of Canine Glomerular Hemodynamics

Kramer

Horáček

Bäcker

et al. 2004

Kidney Blood Press Res

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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^ω-nitro-L-arginine methyl ester hydrochloride (L-NAME), a competitive NO synthase (NOS) inhibitor, the cyclooxygenase inhibitor indomethacin (INDO), and the AT₁ receptor blocker EXP 3174. An intrarenal arterial (i.r.a.) bolus (within 5 min) of 2.5 mg of L-NAME led to a significant decrease in total renal blood flow (RBF) and single nephron glomerular blood flow (SNGBF) from 4.46 ± 0.51 to 3.52 ± 0.41 ml/min/g kidney weight and from 0.393 ± 0.041 to 0.341 ± 0.037 µl/min (p < 0.01), respectively, without a change in glomerular filtration rate (GFR). The increase in arteriolar resistance was more pronounced at the efferent (+31%) than at the afferent (+13%) arteriole, and K_f decreased from 4.5 ± 0.5 to 3.7 ± 0.4 nl/min/mm Hg (p < 0.01). INDO (5 mg/kg i.v. bolus followed by 0.17 mg/kg/min i.v.) had no effect on glomerular hemodynamics. EXP 3174 (30 µg/kg/min i.r.a.) increased RBF and SNGBF from 4.35 ± 0.45 to 4.99 ± 0.50 ml/min/g kidney weight and from 0.403 ± 0.028 to 0.478 ± 0.039 µl/min (p < 0.01), respectively, without an effect on GFR. It reduced the efferent arteriolar resistance by 25% as compared to 13% at the afferent arteriolar level. EXP 3174 increased K_f from 5.1 ± 0.4 to 8.1 ± 0.6 mm Hg (p < 0.01) in the presence of a decrease in effective filtration pressure from 13.2 ± 1.7 to 8.3 ± 1.0 mm Hg (p < 0.01). The glomerular hemodynamic effects of L-NAME were unaltered by pretreatment with INDO or EXP 3174, whereas its tubular effects were restored in the presence of EXP 3174. Thus, from these first micropuncture data in the anesthetized dog on a normal sodium intake we conclude that (1) acute intrarenal inhibition of NOS by L-NAME decreases RBF and SNGBF due to vasoconstriction of the afferent and, more pronounced, efferent arterioles. Since L-NAME simultaneously decreases K_f, GFR remains unaltered. (2) These renal hemodynamic effects of NOS inhibition were not mediated by prostanoids or intrarenal ANG II. Thus, the tonic activity of intrarenal NOS plays an important role in maintaining glomerular hemodynamics in the canine kidney.

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Section: Experimental Techniquesmentioning

confidence: 99%

Relative Roles of Nitric Oxide, Prostanoids and Angiotensin II in the Regulation of Canine Glomerular Hemodynamics

Kramer

Horáček

Bäcker

et al. 2004

Kidney Blood Press Res

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“…In the kidney, most authors agree that kinins contribute to renal vasodilatory actions of ACE inhibitors in animals subjected to hypovolemia or a low-sodium diet [5][6][7][8][9], ie, to conditions known to activate the RAS and kallikrein-kinin system [10]. The role of kinins seems to be particularly important in the effects of ACE inhibitors on the medullary circulation [6,9].…”

Section: Interactions With Other Local and Circulating Renal Humoral mentioning

confidence: 96%

Optimal strategies for preventing progression of renal disease: Should angiotensin converting enzyme inhibitors and angiotensin receptor blockers be used together?

Komers

Anderson

2000

Current Science Inc

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Interruption of the renin-angiotensin system (RAS) with angiotensin converting enzyme (ACE) inhibitors or angiotensin AT(1) receptor blockers has been shown to delay progression in a variety of renal diseases, suggesting that the RAS, and its major effector molecule, angiotensin II, are important players in renal pathophysiology. Both antagonists combine inhibition of deleterious effects of angiotensin II with activation of potentially beneficial pathways mediated by nitric oxide and prostaglandins. Some concerns have been raised about the completeness of the RAS blockade achieved by these agents. ACE-independent pathways can generate angiotensin II, whereas increases in angiotensin II levels may compete with the AT(1) receptor blocker at the receptor site. It has been suggested that an ACE inhibitor/AT(1) receptor blocker combination offers a better therapeutic effect than treatment with either agent alone. In this review, we focus on mechanisms of actions of ACE inhibitors and AT(1) receptor blockers, implicate them in the rationale for the use of an ACE inhibitor/AT(1) receptor blocker combination, and discuss evidence evaluating the renal effects of the combination as compared to the effects of a single agent. There is a surprising lack of information about the nephroprotective potential of the combination, allowing no consistent conclusions about the superiority of the combination over the single agent. Several experimental and clinical reports suggest that in some conditions, the combination may be beneficial. Rather than providing unequivocal evidence for the use of combination treatment in the renal disease, these studies should be considered as stimuli for more detailed exploration of this issue.

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“…However, renal hemodynamic [96] in normal animals was not altered by the BK-B 2 antagonists, HOE 140, or D-Arg 0 [Hyp 3 ,Thi 5,8 , D-Phe 7 ]BK (Thi 5,8 -BK) [96,97,98,99]. In the same way, in normotensive rats, increased renal blood flow caused by the ACE inhibitor, captopril, was not altered by treatment with Thi 5.8 -BK [100].…”

Section: What Is the Renal Kallikrein-kinin System (Renal Kks)? Ismentioning

confidence: 99%

A Novel Category of Anti-Hypertensive Drugs for Treating Salt-Sensitive Hypertension on the Basis of a New Development Concept

Katori

Murakami

2010

Pharmaceuticals

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Terrestrial animals must conserve water and NaCl to survive dry environments. The kidney reabsorbs 95% of the sodium filtered from the glomeruli before sodium reaches the distal connecting tubules. Excess sodium intake requires the renal kallikrein-kinin system for additional excretion. Renal kallikrein is secreted from the distal connecting tubule cells of the kidney, and its substrates, low molecular kininogen, from the principal cells of the cortical collecting ducts (CD). Formed kinins inhibit reabsorption of NaCl through bradykinin (BK)-B2 receptors, localized along the CD. Degradation pathway of BK by kinin-destroying enzymes in urine differs completely from that in plasma, so that ACE inhibitors are ineffective. Urinary BK is destroyed mainly by a carboxypeptidase-Y-like exopeptidase (CPY) and partly by a neutral endopeptidase (NEP). Inhibitors of CPY and NEP, ebelactone B and poststatin, respectively, were found. Renal kallikrein secretion is accelerated by potassium and ATP-sensitive potassium (KATP) channel blockers, such as PNU-37883A. Ebelactone B prevents DOCA-salt hypertension in rats. Only high salt intake causes hypertension in animals deficient in BK-B2 receptors, tissue kallikrein, or kininogen. Hypertensive patients, and spontaneously hypertensive rats, excrete less kallikrein than normal subjects, irrespective of races, and become salt-sensitive. Ebelactone B, poststatin, and KATP channel blockers could become novel antihypertensive drugs by increase in urinary kinin levels. Roles of kinin in cardiovascular diseases were discussed.

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

Cited by 19 publications

References 20 publications

Relative Roles of Nitric Oxide, Prostanoids and Angiotensin II in the Regulation of Canine Glomerular Hemodynamics

Relative Roles of Nitric Oxide, Prostanoids and Angiotensin II in the Regulation of Canine Glomerular Hemodynamics

Optimal strategies for preventing progression of renal disease: Should angiotensin converting enzyme inhibitors and angiotensin receptor blockers be used together?

A Novel Category of Anti-Hypertensive Drugs for Treating Salt-Sensitive Hypertension on the Basis of a New Development Concept

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