Tonic and phasic influences of nitric oxide on renal blood flow autoregulation in conscious dogs

Just, Armin; Ehmke, Heimo; Wittmann, U.; Kirchheim, H. R.

doi:10.1152/ajprenal.1999.276.3.f442

Cited by 33 publications

(58 citation statements)

References 19 publications

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“…It should be noted that the present finding does not contradict a regulatory role for NO, operating in conjunction with the TGF (47) or mesangial chloride concentrations (46), because the present findings were made after blockade of the TGF by furosemide. In this respect, there is also no conflict with our previous finding of a phasic regulatory role of NO in RBF autoregulation (27). The present results rather suggest that the latter effect may be due to a TGFassociated mechanism.…”

Section: Time Coursecontrasting

confidence: 63%

“…In addition, in a previous study (27) the clamping of plasma levels of NO by a very similar protocol indeed had an effect on the autoregulation of RBF. It should be noted that the present finding does not contradict a regulatory role for NO, operating in conjunction with the TGF (47) or mesangial chloride concentrations (46), because the present findings were made after blockade of the TGF by furosemide.…”

Section: Time Coursementioning

confidence: 62%

“…A reasonable possibility would have been some action of endogenous NO, because a previous investigation had revealed an important modulatory influence of NO on humorally induced vasoconstrictor tone in the kidney (8), and other observations had suggested a role of phasic changes in this dilator substance in dynamic autoregulation of RBF (27). However, clamping of the plasma levels of NO did not induce any alteration of the level of RVR during the plateau compared with furosemide alone.…”

Section: Time Coursementioning

confidence: 97%

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Dynamic characteristics and underlying mechanisms of renal blood flow autoregulation in the conscious dog

Just

Ehmke

Toktomambetova

et al. 2001

American Journal of Physiology-Renal Physiology

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The time course of the autoregulatory response of renal blood flow (RBF) to a step increase in renal arterial pressure (RAP) was studied in conscious dogs. After RAP was reduced to 50 mmHg for 60 s, renal vascular resistance (RVR) decreased by 50%. When RAP was suddenly increased again, RVR returned to baseline with a characteristic time course (control; n = 15): within the first 10 s, it rose rapidly to 70% of baseline ( response 1), thus already comprising 40% of the total RVR response. Thereafter, it increased at a much slower rate until it started to rise rapidly again at 20–30 s after the pressure step ( response 2). After passing an overshoot of 117% at 43 s, RVR returned to baseline values. Similar responses were observed after RAP reduction for 5 min or after complete occlusions for 60 s. When tubuloglomerular feedback (TGF) was inhibited by furosemide (40 mg iv, n = 12), response 1 was enhanced, providing 60% of the total response, whereas response 2 was completely abolished. Instead, RVR slowly rose to reach the baseline at 60 s ( response 3). The same pattern was observed when furosemide was given at a much higher dose (>600 mg iv; n = 6) or in combination with clamping of the plasma levels of nitric oxide ( n = 6). In contrast to RVR, vascular resistance in the external iliac artery after a 60-s complete occlusion started to rise with a delay of 4 s and returned to baseline within 30 s. It is concluded that, in addition to the myogenic response and the TGF, a third regulatory mechanism significantly contributes to RBF autoregulation, independently of nitric oxide. The three mechanisms contribute about equally to resting RVR. The myogenic response is faster in the kidney than in the hindlimb.

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Section: Time Coursecontrasting

confidence: 63%

Section: Time Coursementioning

confidence: 62%

Section: Time Coursementioning

confidence: 97%

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Dynamic characteristics and underlying mechanisms of renal blood flow autoregulation in the conscious dog

Just

Ehmke

Toktomambetova

et al. 2001

American Journal of Physiology-Renal Physiology

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“…In our laboratory, we demonstrated that impaired RBF autoregulation in the contralateral kidney of two-kidney, one-clip (2K1C) Goldblatt hypertensive rats was improved by NO synthesis inhibition (27). In line with these observations is enhancement of tubuloglomerular feedback during NO synthesis inhibition (8,28), enhancement of myogenic contractions with increases in perfusion pressure in the juxtamedullary nephron preparation (14), and enhancement of the myogenic component of dynamic autoregulation in dogs (17). Nevertheless, there is ongoing debate as to whether autoregulation is modulated by NO.…”

mentioning

confidence: 75%

NO dependency of RBF and autoregulation in the spontaneously hypertensive rat

Racasan

Joles

Boer

et al. 2003

American Journal of Physiology-Renal Physiology

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. NO dependency of RBF and autoregulation in the spontaneously hypertensive rat. Am J Physiol Renal Physiol 285: F105-F112, 2003. First published March 11, 2003 10.1152/ajprenal.00348.2002In the spontaneously hypertensive rat (SHR), renal blood flow (RBF) has been reported to be very dependent on nitric oxide (NO); however, autoregulation is normal, albeit shifted to higher perfusion pressures. To test the hypothesis that in the SHR NO dependency of RBF autoregulation is diminished, we investigated RBF autoregulation in anesthetized young male SHR and normotensive Wistar-Kyoto (WKY) rats before and during acute intravenous NO synthase (NOS) inhibition with N -nitro-L-arginine (L-NNA) and urinary excretion of nitrate plus nitrite (U NOxV) at different renal perfusion pressures (RPP). Under baseline conditions, SHR had higher mean arterial pressure (147 Ϯ 4 mmHg) and renal vascular resistance (16 Ϯ 1 U) than WKY (105 Ϯ 4 mmHg and 10 Ϯ 0.5 U, respectively, P Ͻ 0.05). RBF was similar (9.4 Ϯ 0.5 vs. 10.3 Ϯ 0.1 ml ⅐ min Ϫ1 ⅐ g kidney wt Ϫ1 ). Acute NOS blockade increased mean arterial pressure similarly, but there was significantly more reduction in RBF and hence an enhanced increase in renal vascular resistance in SHR (to 36 Ϯ 3 vs. 17 Ϯ 1 U in WKY, P Ͻ 0.001). The renal vasculature of SHR is thus strongly dependent on NO in maintaining basal RBF. The lower limit of autoregulation was higher in SHR than WKY in the baseline situation (85 Ϯ 3 vs. 71 Ϯ 2 mmHg, P Ͻ 0.05). Acute L-NNA administration did not decrease the lower limit in the SHR (to 81 Ϯ 3 mmHg, not significant) and decreased the lower limit to 63 Ϯ 2 mmHg (P Ͻ 0.05) in the WKY. The degree of compensation as a measure of autoregulatory efficiency attained at spontaneous perfusion pressures was comparable in SHR vs. WKY but with a shift of the curve toward higher perfusion pressures in SHR. Acute NOS blockade only increased the degree of compensation in WKY. Remarkably, UNOxV was significantly lower at spontaneous RPP in SHR. After reduction of RPP, the observed decrease in UNOxV was significantly more pronounced in WKY than in SHR. In conclusion, the renal circulation in SHR is dependent on high levels of NO; however, the capacity to modulate NO in response to RPP-induced changes in shear stress seems to be limited. urinary excretion; renal perfusion pressures THE KIDNEY'S INTRINSIC property to regulate vascular tone so that renal blood flow (RBF) and glomerular filtration rate (GFR) remain relatively constant during perturbations of renal perfusion pressure (RPP) protects the tubular system from rapid changes in filtered load (7,24). On the basis of several observations, it seems likely that nitric oxide (NO) release, depending on perfusion pressure-dependent variations in shear stress, can also dynamically modulate renal vascular tone. Endothelial NO synthase (NOS) is present in the preglomerular vasculature, and the afferent arteriole has been demonstrated to constrict on inhibition of NO synthesis (15). Thus one would anticipate that with a gradual incr...

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“…The CB PO 2 and chemoreceptor discharges were affected by hemorrhagic hypotension only when arterial blood pressure fell below 50 Torr, and then CB PO 2 decreased producing chemosensory excitation. The lack of a significant effect of hypotension indicates that O 2 delivery to CB was almost independent of the systemic blood pressure above 50 Torr, suggesting that CB microcirculation and PO 2 are regulated by an intrinsic mechanism, which may be partially mediated by NO as is the case in other vascular beds (23,24). However, the mechanisms underlying the blood flow autoregulation in the CB remain to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of NO on carotid body: contribution of neural and endothelial nitric oxide synthase isoforms

Valdés

Mosqueira

Rey

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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Valdé s, Viviana, Matías Mosqueira, Sergio Rey, Rodrigo Del Rio, and Rodrigo Iturriaga. Inhibitory effects of NO on carotid body: contribution of neural and endothelial nitric oxide synthase isoforms. Am J Physiol Lung Cell Mol Physiol 284: L57-L68, 2003. First published September 6, 2002 10.1152/ajplung.00494.2001.-We tested the hypothesis that nitric oxide (NO) produced within the carotid body is a tonic inhibitor of chemoreception and determined the contribution of neuronal and endothelial nitric oxide synthase (eNOS) isoforms to the inhibitory NO effect. Accordingly, we studied the effect of NO generated from S-nitroso-Nacetylpenicillamide (SNAP) and compared the effects of the nonselective inhibitor N -nitro-L-arginine methyl ester (L-NAME) and the selective nNOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole (TRIM) on chemosensory dose-response curves induced by nicotine and NaCN and responses to hypoxia (PO2 Ϸ 30 Torr). CBs excised from pentobarbitoneanesthetized cats were perfused in vitro with Tyrode at 38°C and pH 7.40, and chemosensory discharges were recorded from the carotid sinus nerve. SNAP (100 M) reduced the responses to nicotine and NaCN. L-NAME (1 mM) enhanced the responses to nicotine and NaCN by increasing their duration, but TRIM (100 M) only enhanced the responses to high doses of NaCN. The amplitude of the response to hypoxia was enhanced by L-NAME but not by TRIM. Our results suggest that both isoforms contribute to the NO action, but eNOS being the main source for NO in the cat CB and exerting a tonic effect upon chemoreceptor activity. chemoreceptor; nitric oxide THE VENTILATORY EFFECTS of nitric oxide (NO) and the role played by nitric oxide synthase (NOS) isoforms are complex (14,18,30). In the nucleus tractus solitarii, NO plays a significant excitatory role in sustaining the ventilatory response to hypoxia (14,18,35). However, several lines of evidence indicate that NO produced within the carotid body (CB) is an inhibitory modulator of hypoxic chemoreception (2,8,20,25,34,38). The administration of the precursor L-arginine, NO donor molecules (8,22,38), and NO gas (20) to the cat CB perfused in vitro reduces the chemosensory response to hypoxia. On the other hand, the inhibition of NOS increases the frequency of carotid chemosensory discharges (f x ) in the cat CB in situ and in vitro (19,38). However, little is known about the effects of NO on chemosensory responses induced by other excitatory stimuli, such as nicotine and NaCN. In a previous paper, we found that the NO donor sodium nitroprusside (SNP) reversibly reduced chemosensory responses induced by single doses of NaCN and nicotine in the superfused cat CB (2). In anesthetized cats, the NOS inhibitor N -nitro-L-arginine methyl ester (L-NAME) increased basal f x and enhanced responses to NaCN and dopamine (19). These results suggest that, besides the well-known inhibitory effect of NO on hypoxic chemoreception, NO may also modulate the responses to other stimuli.In the cat CB, NOS immunoreactivity and diaphorase activitie...

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Tonic and phasic influences of nitric oxide on renal blood flow autoregulation in conscious dogs

Cited by 33 publications

References 19 publications

Dynamic characteristics and underlying mechanisms of renal blood flow autoregulation in the conscious dog

Dynamic characteristics and underlying mechanisms of renal blood flow autoregulation in the conscious dog

NO dependency of RBF and autoregulation in the spontaneously hypertensive rat

Inhibitory effects of NO on carotid body: contribution of neural and endothelial nitric oxide synthase isoforms

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