scholarly journals Rho kinase (ROCK) inhibition counteracts tyrosine kinase inhibitor‐induced rise in arterial pressure and renal vascular resistance

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Olaf Grisk ◽  
Thomas Meissner ◽  
Alexander Donner ◽  
Diana Braun ◽  
Uwe Zimmermann ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Vascular Resistance ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Renal Vascular Resistance ◽  
Rock Inhibition ◽  
Renal Vascular

Vasoconstrictor and vasodilator sites within anteroventral third ventricle region

1987 ◽  
Vol 253 (6) ◽  
pp. R827-R831 ◽  
Author(s):  
M. L. Mangiapane ◽  
M. J. Brody
Keyword(s):  
Electrical Stimulation ◽  
Arterial Pressure ◽  
Vascular Resistance ◽  
Third Ventricle ◽  
Renal Vascular Resistance ◽  
Preoptic Nucleus ◽  
Median Preoptic Nucleus ◽  
Tungsten Microelectrode ◽  
Renal Vascular ◽  
Stimulation Of

Previous studies have shown that electrical stimulation of the rat anteroventral third ventricle (AV3V) region produces a characteristic pattern of hemodynamic effects, i.e., renal and mesenteric vasoconstriction, and hindquarters vasodilation. In the present study, we localized the vasoconstrictor and vasodilator effects to specific subregions of the AV3V. In urethan-anesthetized rats prepared with arterial catheters and pulsed Doppler flow probes, we assessed the effects of electrical stimulation of four nuclei within AV3V on mean arterial pressure and renal, mesenteric, and hindquarters resistance. These nuclei were the organum vasculosum lamina terminalis (OVLT), ventral nucleus medianus (median preoptic nucleus), anterior (precommissural) nucleus medianus (median preoptic nucleus), and periventricular preoptic nuclei. Stimulation was carried out by use of a tungsten microelectrode. Stimulation of the OVLT consistently provoked stimulus-locked increases in arterial pressure coupled with increases in mesenteric and renal vascular resistance. Ganglionic blockade with chlorisondamine prevented these responses, demonstrating that they were mediated neurogenically. Stimulation of the three remaining nuclei produced decreases in arterial pressure, hindquarters vasodilation, and little change in mesenteric and renal vascular resistance. No changes in heart rate were observed with stimulation of any of the four nuclei. These results suggest that the vasoconstrictor and pressor functions of the AV3V region are localized in or near the OVLT region, whereas the remaining nuclei of the AV3V region mediate vasodilator and depressor responses.

Effects of a new dihydropyridine derivative, S12968 (pranedipine), and its stereoisomer, S12967, on renal effects of endothelin-1

1994 ◽  
Vol 72 (11) ◽  
pp. 1294-1298 ◽  
Author(s):  
Immaculada Montañés ◽  
Olga Flores ◽  
Nélida Eleno ◽  
José M. López-Novoa
Keyword(s):  
Renal Function ◽  
Arterial Pressure ◽  
Vascular Resistance ◽  
Fold Increase ◽  
Urine Flow ◽  
Renal Vascular Resistance ◽  
Potassium Excretion ◽  
Endothelin 1 ◽  
Dihydropyridine Derivative ◽  
Renal Vascular

The purpose of the present study was to assess in rats the prevention by two enantiomers of a new dihydropyridine derivative (pranedipine) (called S12967 for the dextrogyre(+) and S12968 for the levogyre (−) molecules) of the renal and cardiovascular effects induced by endothelin-1. The injection of endothelin-1 (1 nmol/kg body weight) induced a sharp and transient decrease in urine flow, sodium and potassium excretion, glomerular filtration rate, renal plasma flow, and renal blood flow, a significant increase in renal vascular resistance, and a small but significant increase in arterial pressure. Treatment with S12968 alone (0.3 mg/kg) induced a 2.5-fold increase in urine flow and potassium excretion and a 4.5-fold increase in sodium excretion. Pretreatment with S12968 completely blocked the endothelin-1 induced increase in arterial pressure, did not affect the acute effect of endothelin-1 on urine flow, sodium and potassium excretion, filtration rate, and renal blood flow, but blunted the effect on renal vascular resistance. Administration of S12967 alone (1 mg/kg) did not induce changes in either renal function or arterial pressure. In S12967-treated animals, endothelin-1 also induced a transient increase in arterial pressure and renal vascular resistance but failed to change renal function in a significant manner. In summary, the above reported experiments show that at the higher, nonhypotensive doses, the levogyre enantiomer (S12968) of a new dihydropyridine derivative (pranedipine) completely prevented the hypertensive effect of endothelin 1, and partially prevented the effect of endothelin-1 on renal vascular resistance. The dextrogyre enantiomer (S12967) had almost no effect on either mean arterial pressure or renal vascular resistance but completely blocked the endothelin-1-induced decrease in urine flow and urinary sodium excretion.Key words: calcium antagonists, endothelin, dihydropyridines, kidney, renal function (rat).

scholarly journals Losartan does not decrease renal oxygenation and norepinephrine effects in rats after resuscitated hemorrhage

2018 ◽  
Vol 315 (2) ◽  
pp. F241-F246
Author(s):  
Sofia Jönsson ◽  
Jacqueline M. Melville ◽  
Mediha Becirovic-Agic ◽  
Michael Hultström
Keyword(s):  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Oxygen Tension ◽  
Vascular Resistance ◽  
Renal Vascular Resistance ◽  
Renal Oxygen Consumption ◽  
Significant Difference ◽  
Renal Vascular

Renin-angiotensin-system blockers are thought to increase the risk of acute kidney injury after surgery and hemorrhage. We found that losartan does not cause renal cortical hypoxia after hemorrhage in rats because of decreased renal vascular resistance, but we did not evaluate resuscitation. We aimed to study losartan’s effect on renal cortical and medullary oxygenation, as well as norepinephrine’s vasopressor effect in a model of resuscitated hemorrhage. After 7 days of losartan (60 mg·kg−1·day−1) or control treatment, male Wistar rats were hemorrhaged 20% of their blood volume and resuscitated with Ringerʼs acetate. Mean arterial pressure, renal blood flow, and kidney tissue oxygenation were measured at baseline and after resuscitation. Finally, the effect of norepinephrine on mean arterial pressure and renal blood flow was investigated. As expected, losartan lowered mean arterial pressure but not renal blood flow. Losartan did not affect renal oxygen consumption and oxygen tension. Mean arterial pressure and renal blood flow were lower after resuscitated hemorrhage. A smaller increase of renal vascular resistance in the losartan group translated to a smaller decrease in cortical oxygen tension, but no significant difference was seen in medullary oxygen tension, either between groups or after hemorrhage. The effect of norepinephrine on mean arterial pressure and renal blood flow was similar in control- and losartan-treated rats. Losartan does not decrease renal oxygenation after resuscitated hemorrhage because of a smaller increase in renal vascular resistance. Further, losartan does not decrease the efficiency of norepinephrine as a vasopressor, indicating that blood pressure may be managed effectively during losartan treatment.

Evidence for endothelin-induced renal vasoconstriction independent of ETA receptor activation

1993 ◽  
Vol 264 (1) ◽  
pp. R222-R226 ◽  
Author(s):  
D. M. Pollock ◽  
T. J. Opgenorth
Keyword(s):  
Glomerular Filtration Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Vascular Resistance ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Renal Vascular Resistance ◽  
Renal Vascular

Experiments were designed to examine the role of endothelin (ET) receptors, specifically ETA receptors, in mediating the renal vasoconstrictor effects of ET-1 in anesthetized Sprague-Dawley rats. Intravenous infusion of ET-1 at 25 pmol.kg-1 x min-1 for 60 min produced a significant increase in mean arterial pressure (20 +/- 7%) and decreases in renal plasma flow (-60 +/- 6%) and glomerular filtration rate (-47 +/- 6%). Renal vascular resistance was significantly increased from 17 +/- 1 mmHg.ml-1 x min.g kidney wt during control period to 54 +/- 11 mmHg.ml-1 x min.g kidney wt during the experimental period. A second group of rats was infused with both ET-1 and the specific ETA receptor antagonist BQ-123 (0.1 mg.kg-1 x min-1). ET-1-induced increases in mean arterial pressure were completely blocked by BQ-123 (the average change was -7 +/- 4%). However, the renal vasoconstrictor effects of ET-1 were not affected by the antagonist, since renal plasma flow and glomerular filtration rate were again significantly reduced (-54 +/- 4 and -56 +/- 6%, respectively). Once again, renal vascular resistance was significantly increased from 16 +/- 2 mmHg.ml-1 x min.g kidney wt during the control period to 33 +/- 5 mmHg.ml-1 x min.g kidney wt during the experimental period. In a third group, infusion of BQ-123 alone produced a significant decline in mean arterial pressure (-13 +/- 2%), with no significant changes in renal plasma flow or glomerular filtration rate, thus producing a significant decrease in renal vascular resistance (15 +/- 1 vs. 11 +/- 2 mmHg.ml-1 x min.g kidney wt).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of pulmonary vasodilator responses to the Rho-kinase inhibitor fasudil in the anesthetized rat

2008 ◽  
Vol 295 (5) ◽  
pp. L828-L836 ◽  
Author(s):  
Adeleke M. Badejo ◽  
Jasdeep S. Dhaliwal ◽  
David B. Casey ◽  
Thomas B. Gallen ◽  
Anthony J. Greco ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Systemic Arterial Pressure ◽  
Prior Exposure ◽  
Intravenous Injections ◽  
Pulmonary Vasodilator

The small GTP-binding protein Rho and its downstream effector, Rho-kinase, are important regulators of vasoconstrictor tone. Rho-kinase is upregulated in experimental models of pulmonary hypertension, and Rho-kinase inhibitors decrease pulmonary arterial pressure in rodents with monocrotaline and chronic hypoxia-induced pulmonary hypertension. However, less is known about responses to fasudil when pulmonary vascular resistance is elevated on an acute basis by vasoconstrictor agents and ventilatory hypoxia. In the present study, intravenous injections of fasudil reversed pulmonary hypertensive responses to intravenous infusion of the thromboxane receptor agonist, U-46619 and ventilation with a 10% O2 gas mixture and inhibited pulmonary vasoconstrictor responses to intravenous injections of angiotensin II, BAY K 8644, and U-46619 without prior exposure to agonists, which can upregulate Rho-kinase activity. The calcium channel blocker isradipine and fasudil had similar effects and in small doses had additive effects in blunting vasoconstrictor responses, suggesting parallel and series mechanisms in the lung. When pulmonary vascular resistance was increased with U-46619, fasudil produced similar decreases in pulmonary and systemic arterial pressure, whereas isradipine produced greater decreases in systemic arterial pressure. The hypoxic pressor response was enhanced by 5–10 mg/kg iv nitro-l-arginine methyl ester (l-NAME), and fasudil or isradipine reversed the pulmonary hypertensive response to hypoxia in control and in l-NAME-treated animals, suggesting that the response is mediated by Rho-kinase and L-type Ca2+ channels. These results suggest that Rho-kinase is constitutively active in regulating baseline tone and vasoconstrictor responses in the lung under physiological conditions and that Rho-kinase inhibition attenuates pulmonary vasoconstrictor responses to agents that act by different mechanisms without prior exposure to the agonist.

Effect of Change in Flow Rate Upon Renal Vascular Resistance

1958 ◽  
Vol 195 (1) ◽  
pp. 111-119 ◽  
Author(s):  
F. J. Haddy ◽  
J. Scott ◽  
M. Fleishman ◽  
D. Emanuel
Keyword(s):  
Arterial Pressure ◽  
Vascular Resistance ◽  
Flow Rate ◽  
Blood Flow Rate ◽  
Renal Vascular Resistance ◽  
Renal Nerves ◽  
Local Mechanism ◽  
Anesthetized Dogs ◽  
Renal Flow ◽  
Renal Vascular

The effect of changing renal flow rate upon renal vascular resistance has been studied in 82 anesthetized dogs. Resistance decreased and then increased as a function of blood flow rate. The onset of the increase in resistance was more dependent upon flow rate than arterial pressure. These relationships were unaltered by section of renal nerves, infusion of phentolamine, infusion of phentolamine and eserine and ventilation with 20% CO2. The increase in resistance remained following decapsulation but began at lower levels of flow rate and pressure. The increase in resistance was absent during perfusion with blood when dextran was intermittently used as the perfusate, during perfusion with dextran in live or dead kidneys and during perfusion with blood in dead kidneys. Elevation of arterial pressure failed to greatly elevate the flow rate of renal lymph. These observations indicate that the increase in resistance results from active vasoconstriction initiated by some local mechanism which is independent of nerves, circulating adrenalines, CO2 tension and [H+]. The mechanism likely is activated by change in flow rate.

NO dependency of RBF and autoregulation in the spontaneously hypertensive rat

2003 ◽  
Vol 285 (1) ◽  
pp. F105-F112 ◽  
Author(s):  
Simona Racasan ◽  
Jaap A. Joles ◽  
Peter Boer ◽  
Hein A. Koomans ◽  
Branko Braam
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Lower Limit ◽  
Vascular Resistance ◽  
Spontaneously Hypertensive Rat ◽  
Renal Vascular Resistance ◽  
Renal Vasculature ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Renal Vascular

In 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 Nω-nitro-l-arginine (l-NNA) and urinary excretion of nitrate plus nitrite (UNOxV) at different renal perfusion pressures (RPP). Under baseline conditions, SHR had higher mean arterial pressure (147 ± 4 mmHg) and renal vascular resistance (16 ± 1 U) than WKY (105 ± 4 mmHg and 10 ± 0.5 U, respectively, P < 0.05). RBF was similar (9.4 ± 0.5 vs. 10.3 ± 0.1 ml · min-1 · g kidney wt-1). 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 ± 3 vs. 17 ± 1 U in WKY, P < 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 ± 3 vs. 71 ± 2 mmHg, P < 0.05). Acute l-NNA administration did not decrease the lower limit in the SHR (to 81 ± 3 mmHg, not significant) and decreased the lower limit to 63 ± 2 mmHg ( P < 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.

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