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M Steinhausen

Publications and source records attributed to M Steinhausen.

At least 19 recordsLinked to original sources
PubMed2000

In vivo effects of diadenosine polyphosphates on rat renal microcirculation.

BACKGROUND: Diadenosine polyphosphates (APXA) are vasoactive nucleotides that elicit effects via purinoceptors. Recent data suggest differential effects of APXA on kidney vasculature. METHODS: The in vivo effects of AP3A, AP5A, and adenosine on renal microvessels and the role of purinoceptors were investigated by the application of agonists to the hydronephrotic rat kidney and preincubation with respective antagonists. RESULTS: The addition of the agonists (10-7 mol/L up to 10-4 mol/L) resulted in a concentration-dependent transient vasoconstriction [interlobular artery (ILOB): adenosine 30 +/- 7%, N = 7, AP3A 35 +/- 10%, N = 5; AP5A 66 +/- 19%, N = 5; 10-5 mol/L each] lasting up to one minute, followed by a concentration-dependent vasodilation (ILOB: adenosine 10 +/- 3%, N = 6; AP3A 19 +/- 4%, N = 5; AP5A 12 +/- 5%, N = 6; 10-5 mol/L each). In ILOB and in the afferent arteriole (AFF), the constrictory effects of AP5A were more pronounced than those of AP3A and adenosine. In the efferent arteriole (EFF), vascular tone was only slightly affected by all agonists. The dilatory potency was comparable for all agonists in ILOB and EFF. No significant vasodilation occurred in AFF. The application of the selective A1 receptor antagonist DPCPX (10-5 mol/L) completely abolished the adenosine-induced vasoconstriction, whereas the A2 receptor antagonist DMPX and the P2 purinoceptor antagonists PPADS and A3P5P (all 10-5 mol/L) did not affect adenosine-induced constriction. The AP3A-induced constriction was abolished by DPCPX and was partially inhibited by PPADS. The constriction induced by AP5A was less sensitive to DPCPX but more sensitive to PPADS. In ILOB and EFF, DMPX or A3P5P abolished dilation after the addition of the agonists. The dilation after AP5A was not significantly reduced. In AFF, no significant dilation was observed with these agonists alone, but it was clearly visible in the presence of DPCPX or PPADS. CONCLUSIONS: APXA evoke transient constrictions in vessels of the hydronephrotic rat kidney, which are mediated by A1 and P2 purinoceptors. The length of the phosphate chain determines the degree of vasoconstriction and the extent to which the substances exert effects on the P2 purinoceptor subtypes. ILOB and AFF are more potently affected by APXA than EFF. Afferent vasodilation is partially overridden by sustained vasoconstriction.

Adenosine↗
PubMed1998

Contribution of endothelin receptors in renal microvessels in acute cyclosporine-mediated vasoconstriction in rats.

Cyclosporine A (CsA), a widely used immunosuppressive agent, causes renal vasoconstriction and systemic hypertension. Recent data suggest that the renal effect of CsA is possibly mediated by endothelin (ET). We investigated the effects of CsA on renal microvessels and the efficacy of ETA or ETA/ETB receptor antagonists in ameliorating CsA effects in the hydronephrotic rat kidney. Infusion of CsA (30 mg.kg-1) induced a transient increase (20%) in mean arterial pressure (MAP) and a sustained reduction (85%) in glomerular blood flow (GBF) due to preferential constriction of the arcuate artery (39%) and the proximal segment of the interlobular artery (23%). Under basal conditions the ETA receptor antagonist BQ-123 had marginal effects consisting of reduction in MAP, rise in GBF and dilation of preglomerular vessels. The non-selective ETA/ETB receptor antagonist PD 145065 also reduced MAP, but tended to decrease GBF and constrict large preglomerular vessels. The difference in effects of the two antagonists indicated that under basal conditions ETB blockade constricts large preglomerular vessels and reduces GBF. After BQ-123 or PD 145065, the constriction of large preglomerular vessels and reduction in GBF induced by CsA was attenuated by about 50%, but the rise in MAP was not influenced. Our data indicate that a sizable part of renal vasoconstriction due to CsA is mediated via ET production in large preglomerular arteries and can be avoided by the blockade of ETA receptors. Additional blockade of ETB receptors does not attenuate the CsA effects further, possibly because ETB receptors mediate both vasoconstriction and dilation.

Animals↗
PubMed1997

Electrically induced vasomotor responses and their propagation in rat renal vessels in vivo.

1. Vasomotor responses (VMR) induced by local electrical stimulation were studied in the vasculature of the split hydronephrotic rat kidney by in vivo microscopy. 2. Unipolar pulses, which were applied by a micropipette positioned close to the vessel wall, elicited local and propagated VMR. Depolarizing and hyperpolarizing currents caused vasoconstriction and vasodilatation, respectively. 3. The magnitude of VMR could be controlled within seconds by variation of pulse frequency, pulse width and voltage. VMR were abolished by slight retraction of the stimulating micropipette. Repetitive electrical stimulation resulted in reproducibly uniform VMR. 4. Propagated VMR decayed with increasing distance from the stimulation site. They decayed more rapidly in the upstream than in the downstream flow direction in interlobular arteries. The longitudinal decay was well approximated by an exponential function with significantly different length constants of 150 +/- 40 microns (upstream, n = 5) and 420 +/- 90 microns (downstream, n = 8). 5. Our results show that vasomotor responses, which are initiated by changes in membrane potential, are propagated over distances of potential physiological importance in interlobular arteries.

Animals↗
PubMed1997

Natriuretic peptide receptors mediate different responses in rat renal microvessels.

Atrial natriuretic peptide (ANP) has unique effects on the renal vasculature, in that it dilates preglomerular vessels and constricts efferent arterioles. In the present study we aimed to characterize the natriuretic peptide receptor (NPR) subtypes, which mediate the renovascular effects of ANP, using in vivo microscopy in the split hydronephrotic kidney model of rats. ANP (10(-9) and 3.10(-9)), which binds to NPR-A and NPR-C, dilated preglomerular vessels and constricted efferent arterioles similarly to that found in previous studies. C-type natriuretic peptide (10(-9) to 10(-7)), which binds to NPR-B and NPR-C, dilated pre- and postglomerular vessels and profoundly increased glomerular blood flow. A specific ligand of NPR-C, C-ANP (des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANP 4-23-NH2, 10(-9) to 10(-7)) was devoid of vascular effects. The ANP antagonist A71915 (10(-9) to 10(-6)) induced moderate dilation in renal vessels possibly due to some agonistic activity on NPR-B, ANP-induced preglomerular vasodilation was attenuated by A71915 (10(-6)) to 36 +/- 6% of the initial response, whereas efferent vasoconstriction was completely abolished (-4 +/- 4% of initial response). Our results indicate that ANP dilates preglomerular vessels and constricts efferent arterioles through NPR-A, both responses being antagonized by A71915 with different potencies. Furthermore, our data show that in the rat renal microcirculation stimulation of NPR-B results in vasodilation only, whereas NPR-C does not mediate vascular responses.

Animals↗
PubMed1997

Cardiovascular and renal effects of endothelin receptor blockade with PD 145065 and interaction with urodilatin.

Role of endogenous endothelins (ET) in the control of cardiovascular system and renal function, and ET interaction with urodilatin (URO) were studied in anaesthetized rats. Activity of ET was blocked using PD 145065 (5 mg kg-1 body wt i.v.) a non-selective antagonist of ETA and ETB receptors. PD 145065 decreased mean arterial blood pressure (MBP) from 114 +/- 4 to 109 +/- 4 mmHg and the renal blood flow (RBF) from 6.6 +/- 0.3 to 5.8 +/- 0.4 mL min-1 (P < 0.02) and increased renal vascular resistance (RVR) from 17.7 +/- 1.2 to 20.1 +/- 2.1 mmHg min mL-1. Heart rate (HR) and renal function were not affected. URO was infused i.v. at 0.1 nmol min-1 kg-1 body wt without or with previous ET receptor blockade. After pre-treatment with PD 145065, infusion of URO decreased MBP more than did URO alone: 15 +/- 3% vs. 7 +/- 2% (P < 0.05). RVR and HR did not change after URO alone but decreased with URO given to PD 145065 treated rats (19 +/- 5% and 14 +/- 3%, respectively, P < 0.01). It is concluded that in anaesthetized surgically prepared rats endogenous ET can cause renal vasodilation, in contrast to constriction of systemic vasculature. Enhancement by ET blockade of vascular systemic and renal effects of URO supports ET interaction with natriuretic peptides in the control of cardiovascular and renal function.

Animals↗
PubMed1997

Role of kinins and angiotensin II in the vasodilating action of angiotensin converting enzyme inhibition in rat renal vessels.

OBJECTIVE: To assess directly the vasodilating effects of angiotensin converting enzyme (ACE) inhibition in different renal vessels and to determine the role of kinins and angiotensin II (ANGII) therein. METHODS: Lumen diameters of different vessels and glomerular blood flows were measured in cortical and juxtamedullary glomeruli by in-vivo microscopy in the split hydronephrotic kidney of anesthetized female Wistar rats. RESULTS: Injection of the ACE inhibitor quinapril at a dose of 0.9 mg/kg intravenously, which blocks conversion of locally applied angiotensin I (1 mumol/l), increased glomerular blood flows by 39 +/- 6 and 18 +/- 4% in cortical and juxtamedullary glomeruli, respectively, due to vasodilatation in all renal vessels. The most pronounced vasodilatation was observed in interlobular arteries (19 +/- 2%) and in cortical afferent arterioles (16 +/- 3%). Pretreatment of the hydronephrotic kidney by local application of 40 nmol/l Hoe140, a bradykinin B2 receptor antagonist, or 3 mumol/l valsartan, an ANGII type 1 receptor antagonist, attenuated the vasodilatation in response to quinapril. ANGII receptor blockade affected only weakly, whereas bradykinin receptor blockade blunted markedly, the quinapril-induced vasodilatation, suggesting that kinins play an important role in our experimental model. Administration of valsartan, which abrogated the renal vasoconstriction induced by 10 nmol/l ANGII completely, caused vasodilation of magnitude similar to that caused by administration of quinapril. Yet, the vasodilatation induced by the combination of valsartan and quinapril was significantly larger than that induced by administration of quinapril alone in interlobular arteries, afferent arterioles, and cortical efferent arterioles. CONCLUSIONS: Our results indicate that kinins and ANGII can contribute to the renal vasodilatation in response to ACE inhibitors, but ACE inhibitors appear to have only minor effects on ANGII levels in those renal vessels, which are the well-known sites of renin expression.

Angiotensin II↗
PubMed1997

Organic anion secretion in polycystic kidney disease.

This study examined whether organic anion secretion contributes to fluid accumulation in cysts in polycystic kidney disease. Clearance and micropuncture studies were done on young (7 to 16 wk old), mostly male, heterozygous Han:SPRD cystic rats and healthy control littermate rats. Heterozygous Han:SPRD rats manifest a slowly progressive autosomal dominant polycystic kidney disease that closely resembles the human disorder. Left kidney GFR (polyfructosan clearance), in microl/min per 100 g body wt, averaged 331 +/- 36 (SD) in seven healthy rats and 278 +/- 75 in seven cystic rats. The maximal rate of p-aminohippurate (PAH) secretion, in micromol/min per 100 g body wt, averaged 0.94 +/- 0.24 in healthy rats and 0.83 +/- 0.11 in cystic rats. In these young rats, there were no significant differences in GFR or the maximal rate of PAH secretion despite the presence of cystic disease. Using fluorescence microscopy, it was found that 27 of 29 proximal cysts secreted sulfonefluorescein, an organic anion transported by the PAH system. Transmission electron micrographs of superficial cysts that had secreted sulfonefluorescein demonstrated the presence of both normal-appearing and poorly differentiated proximal tubule cells. Segments of superficial proximal convoluted tubules or cysts, isolated by upstream and downstream wax blocks, failed to accumulate fluid when PAH was infused intravenously. With the stationary microperfusion technique, PAH secretion by both normal and cystic nephrons was demonstrated. It is concluded that most proximal cystic epithelia retain the ability to secrete organic anions. Secretion of organic anions, however, does not appear to contribute in any substantial way to fluid accumulation in cysts in the rat kidney.

Animals↗
PubMed1996

L-selectin activates the Ras pathway via the tyrosine kinase p56lck.

Selectins mediate rolling, the initial step of leukocyte adhesion to endothelial cells [Springer, T. A. (1995) Annu. Rev. Physiol. 57, 827-872 and Butcher, E. C. (1991) Cell 67, 1033-1036]. In this study we show that L-selectin triggering of Jurkat cells using different antibodies or glycomimetics resulted in activation of the src-tyrosine kinase p56lck; tyrosine phosphorylation of intracellular proteins, in particular mitogen-activating protein kinase and L-selectin; and association of Grb2/Sos with L-selectin. This association correlated with an activation of p21Ras, mitogen-activating protein kinase, Rac2, and a transient increase of 2-O synthesis. Stimulation of the Ras pathway by L-selectin requires functional p56lck, since p56lck-deficient Jurkat cells (JCaM1.6) do not show tyrosine phosphorylation, association of L-selectin with Grb2/Sos, and activation of Ras upon L-selectin triggering. Transfection of JCaM1.6 cells with p56lck reconstitutes the observed signaling events. Genetic inhibition of Ras or Rac2 prevented Rac2 stimulation and 2-O synthesis, respectively. The specificity and the physiological significance of the observed signaling cascade is indicated by stimulation of L-selectin-transfected P815, L-selectin-positive CEM or peripheral blood lymphocytes resulting in the same activation events as in Jurkat cells. Our results point to a signaling cascade from L-selectin via p56lck, Grb2/Sos, Ras, and Rac2 to 2-O.

Animals↗
PubMed1996

Localization of endothelin ETA and ETB receptor-mediated constriction in the renal microcirculation of rats.

1. The aim of the study was to visualize endothelin-1 (ET-1)-mediated constriction in renal vessels of cortical and juxtamedullary glomeruli in the split hydronephrotic rat kidney in vivo and to functionally characterize the ET receptor subtypes involved. 2. ET-1 (10(-9) M) constricted preglomerular vessels (by 6-18%) and efferent arterioles (by 11-13%), and decreased glomerular blood flow (GBF, by 55%) of cortical and juxtamedullary glomeruli. 3. The ETA antagonist BQ-123 (10(-6) M), as well as the ETB antagonist BQ-788 (2 x 10(-7) M) and IRL 1038 (10(-6) M), shifted the concentration-response curve of GBF for ET-1 to the right by one order of magnitude. While BQ-123 antagonized ET-1 constriction only in preglomerular vessels, BQ-788 and IRL 1038 were effective both in preglomerular vessels and efferent arterioles. 4. The ETB agonist IRL 1620 (10(-8) M) reduced GBF by 50% and constricted efferent arterioles (by 20-33%) about two times more than preglomerular vessels (by 6-14%). 5. Our results suggest that in renal cortical and juxtamedullary vessels of rats, ET-1-induced preglomerular vasoconstriction is mediated by ETA and ETB receptors, while efferent vasoconstriction is predominantly mediated by ETB receptors, which might have important consequences for the regulation of glomerular filtration pressure by ET.

Animals↗
PubMed1996

Role of obstruction in autosomal dominant polycystic kidney disease in rats.

Kidney micropuncture and microdissection studies were carried out on heterozygous 2- to 4-month-old female and male Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD) and on normal controls, to determine whether cysts are obstructed. Pressures in proximal tubules and cysts were determined using a servo null device and were recorded before, during, and after intraluminal infusion of an isotonic equilibrium solution at 15 and 50 n1/min. Initial cyst pressures in nine cystic rats averaged 18.5 +/- 5.9 (SD) mm Hg, N = 49, significantly (P < 0.01) higher than in normal proximal tubules in four control rats, 14.3 +/- 1.6 mm Hg, N = 36. Pressures in non-cystic tubules in cystic rats, 16.8 +/- 4.4 mm Hg, N = 25, were not significantly different from pressures in control kidneys or in cysts. When proximal tubules were microinfused at 15 nl/min in control rats, tubule pressure increased by 3.8 +/- 1.2 mm Hg, N = 24. In cysts, the response was highly variable. Twenty out of 33 microinfused cysts (61%) showed responses similar to normal tubules and were considered to be nonobstructed; 13 (39%) showed large pressure increases upon microinfusion, sometimes to values over 100 mm Hg (obstructed cysts). Left kidney inulin clearance (in microliter/min. 100 g body wt) averaged 335 +/- 65 (N = 4) in control rats and 344 +/- 144 (N = 9) in cystic rats; at this early stage of the disease no decline in GFR was seen. Weights of cystic kidneys were twice those of normal animals. Microdissection and scanning electron microscopy revealed the presence of intraluminal casts and debris and constrictions between cysts that would impede fluid flow. We conclude that obstruction is a frequent, early event in PKD and, when present, promotes cyst enlargement. Since many cysts are not obstructed, we suggest that factors other than fixed obstruction initiate cyst formation.

Anesthesia↗
PubMed1996

Effect of intrarenally infused parathyroid hormone-related protein on renal blood flow and glomerular filtration rate in the anaesthetized rat.

1. Parathyroid hormone-related protein (PTHrP) is expressed in the kidney and acts on vascular PTH/ PTHrP receptors to vasodilate the isolated kidney and to stimulate renin release. However, effects of PTHrP on renal blood flow (RBF) and glomerular filtration rate (GFR) in vivo have not been assessed in the absence of its cardiac, peripheral and central effects. We investigated the renal effects of PTH and PTHrP infused into the left renal artery of anaesthetized rats. 2. Intrarenal infusions, adjusted to generate increasing concentrations of human PTHrP(1-34) and rat PTH(1-34) in renal plasma (2 x 10(-11) to 6 x 10(-9) M) produced a comparable dose-dependent increase in RBF. The rise was 4% at the lowest and 34% at the highest concentrations of peptides. Up to a concentration of 2 x 10(-9) M, mean arterial pressure (MAP) and heart rate were not affected, but at 6 x 10(-9) M, intrarenally infused peptides reached the peripheral circulation, and caused a fall in MAP within a few minutes. While MAP returned to basal value after the last peptide infusion, RBF remained more than 10% above control for at least 30 min. 3. Two competitive PTH/PTHrP receptor antagonists, [Nle8,18, Tyr34]-bPTH(3-34)amide and [Leu11, D-Trp12]-hPTHrP(7-34)amide (2 x 10(-8) M) were devoid of agonist activity, but markedly antagonized the dose-dependent increase in RBF elicited by PTHrP. 4. GFR and urine flow were measured in left PTHrP-infused experimental kidney and right control kidney. Renal PTHrP concentration of 10(-10) M elevated left RBF by 10%, and GFR by 20% without significantly increasing filtration fraction, and increased urine flow by 57%. In the right control kidney GFR and diuresis did not change. 5. The results indicate that PTHrP has similar renal haemodynamic effects as PTH and increases RBF, GFR and diuresis in anaesthetized rats.

Animals↗
PubMed1996

Nitric oxide modulates angiotensin II- and norepinephrine-dependent vasoconstriction in rat kidney.

This study compared the vasoconstrictor action of angiotensin II (ANG II) and norepinephrine (NE) with different levels of nitric oxide (NO) in the kidney of anesthetized rats. In one series of experiments, the drugs were infused intravenously, and systemic NO content was reduced by a NO synthase inhibitor, nitro-L-arginine methyl ester (L-NAME). L-NAME significantly enhanced the renal blood flow (RBF) reduction produced by ANG II from 26 to 49%, but it had no significant effect on the change in RBF induced by NE. Medullary blood flow was not influenced by either ANG II or NE given alone or given after L-NAME. In the second series of experiments, all drugs were infused into the renal artery to avoid their systemic and, hence, extrarenal effects. In these experiments, renal content of NO was increased by the NO donor sodium nitroprusside (SNP), decreased by L-NAME, or restored by replacing endogenous NO by exogenous NO (L-NAME + SNP). Effects of both ANG II and NE on RBF were similarly and significantly attenuated by SNP (60% of control), enhanced by L-NAME (200% of control), and restored by L-NAME + SNP (90% of control, not significant). Our results indicate that NO attenuates the renal vasoconstriction due to ANG II or NE and that the antagonism between vasoconstrictors and NO is not due to a constrictor-induced production of NO because exogenous and endogenous NO were equally effective.

Angiotensin II↗
PubMed1996

Controversies on glomerular filtration from Ludwig to the present.

Since Ludwig's theory of filtration in the glomerulus is generally accepted, current research interest has focussed on the regulation of this process. The main determinants of glomerular filtration rate are glomerular capillary pressure and glomerular blood flow, which are adjusted via resistance changes in the pre- and postglomerular vasculature. Overall pre- and postglomerular resistances were first determined by micropuncture in superficial glomeruli. While the predominant source of postglomerular resistance is the efferent arteriole, several results indicate that preglomerular resistance might be rather uniformly distributed among all preglomerular vessels (interlobar, arcuate and interlobular arteries and afferent arterioles). Over the last decade, several techniques have been used to visualize renal vessels and to study the action of various vasoactive hormones thereon. Results obtained with the split hydronephrotic kidney model, which permits in vivo microscopy of all renal vessels, provide evidence for a differential regulation of the various preglomerular vessels by vasoactive hormones. In particular, mediators of inflammation almost selectively constrict interlobar and arcuate arteries. We conclude that, given the renal vascular architecture, differential regulation of preglomerular vessels can alter haemodynamic parameters specifically for different nephron populations.

Animals↗
PubMed1995

Vascular effects of parathyroid hormone and parathyroid hormone-related protein in the split hydronephrotic rat kidney.

1. The effects of locally applied parathyroid hormone-related protein (PTHRP), a putative autocrine/paracrine hormone, on vascular diameters and glomerular blood flow (GBF) in the split hydronephrotic rat kidney were studied. As PTHRP interacts with parathyroid hormone (PTH) receptors in all tissues tested so far, the effects of PTHRP were compared with those of PTH. 2. Preglomerular vessels dilated in a concentration- and time-dependent manner that was almost identical for PTH and PTHRP. A significant preglomerular vasodilation (5-17%) occurred at a threshold concentration of 10(-10) mol l-1 PTH or PTHRP, which raised GBF by 20 +/- 2 and 31 +/- 4%, respectively (means +/- S.E.M., n = 6). PTH or PTHRP (10(-7) mol l-1) increased preglomerular diameters (11-36%) and GBF (60 +/- 10 and 70 +/- 8%, respectively) to near maximum. The most prominent dilatation was located at the interlobular artery and at the proximal afferent arteriole. 3. Efferent arterioles were not affected by either PTH or PTHRP. 4. Estimated concentrations of half-maximal response (EC50) for preglomerular vasodilatation and GBF increase were in the nanomolar to subnanomolar range. 5. After inhibition of angiotensin I-converting enzyme by 2 x 10(-6) mol kg-1 quinapril I.V. (n = 6), 10(-8) mol l-1 PTHRP dilated preglomerular vessels and efferent arterioles (9 +/- 1% proximal and 6 +/- 1% distal). 6. We conclude that the renal vasculature of the hydronephrotic kidney is highly sensitive to vasodilatation by PTH and PTHRP, which, in addition, may constrict efferent arterioles by stimulating renin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Effects of urodilatin in the rat kidney: comparison with ANF and interaction with vasoactive substances.

We compared the effects of urodilatin (URO) and atrial natriuretic factor (ANF) in normal and hydronephrotic kidneys (HNK) of rats. Furthermore, the impact of blocking different vasoactive hormones on the action of natriuretic peptides on vessels of cortical (C) and juxtamedullary (JM) glomeruli was studied in HNK by using URO. In normal kidneys, effects of URO and ANF (1.2, 2.4, 4.8, 12, and 19.10(-11) mol.kg-1.min-1 i.v.) were not significantly different. At 12.10(-11) mol.kg-1.min-1, URO and ANF increased urine flow 5.4 +/- 1.7 and 3.0 +/- 0.8-fold, increased urinary sodium excretion 20.7 +/- 8.8 and 10.3 +/- 4.0-fold, and decreased blood pressure by 13 +/- 2% and 12 +/- 1%, respectively (mean +/- SEM). In HNK, URO and ANF (0.4, 0.9, and 2.0.10(-11) mol.kg-1.min-1 i.v. and local application of 0.5, 1.0, and 2.0.10(-9) M) dose-dependent dilated preglomerular vessels (max approximately 20%), constricted efferent arterioles (max approximately 15%), and increased glomerular blood flow of C glomeruli in an identical fashion. Comparing URO effects on C and JM arterioles (0.4 and 0.9.10(-11) mol.kg-1.min-1 i.v.), JM responses were about one third of C responses. Angiotensin converting enzyme inhibition (ACEI, 2.10(-6) mol.kg-1 quinapril i.v.), combined ACEI and cyclooxygenase inhibition (CYOI, 2.8.10(-5) M indomethacin), and endothelin (ET) receptor blockade (10(-6) M BQ 123 and IRL 1038) diminished preglomerular vasodilation (C and JM) caused by URO infusion. Efferent vasoconstriction (C and JM) caused by URO was exaggerated by blockade of nitric oxide synthesis (10(-5) M L-NAME) and abolished by combined ACEI and CYOI, by bradykinin receptor blockade (4.10(-8) M Hoe 140), and by ET blockade. CYOI attenuated only JM efferent constriction. Our results show that URO and ANF possess equipotent vascular and similar natriuretic effects in the rat kidney. The magnitude of preglomerular vasodilation, which is directly mediated by these peptides, depends on the basal level of endogenous vasoconstrictors, while efferent vasoconstriction may be mediated by the secondary release of ET.

Animals↗