Modulation of Circulating Endothelin Levels in Hypertension and Endotoxemia in Rats

Vemulapalli, Subbarao; Chiu, Peter; Rivelli, Maria A.; Foster, Carolyn; Sybertz, Edmund J.

doi:10.1097/00005344-199112000-00017

Cited by 63 publications

(31 citation statements)

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“…It is possible that alterations in medullary blood flow, 28 interstitial pressures, 29 or local hormonal changes 30 could affect production of ET-1 by IMCD cells in SHR, although no such relation between these factors and ET-1 synthesis by IMCD cells has been described. Reduced IMCD ET-1 production could conceivably be due to alterations in circulating plasma ET-1 concentration; however, neither the present study nor previous ones 13 - 14 detected changes in plasma ET-1 in SHR. It is also possible that the reduced ET-1 production is caused by an intrinsic change in IMCD cells.…”

Section: Discussioncontrasting

confidence: 99%

Alterations in renal endothelin-1 production in the spontaneously hypertensive rat.

1992

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Endothelin-1 inhibits sodium and water transport systems in the inner medullary collecting duct Endothelin-1 levels are reduced in the medulla of spontaneously hypertensive rats (SHR), raising the possibility that decreased inner medullary collecting duct production of endothelin-1 could contribute to inappropriate sodium and water retention. In the current study, immunoreactive endothelin-1 was measured in the urine, blood, and eluates from cortex and outer and inner medulla of SHR before (age 3-4 weeks) and after (age 8-9 weeks) the development of hypertension and in age-matched Wistar-Kyoto (WKY) controls. There was no difference in endothelin-1 levels between prehypertensive SHR and WKY rats. In contrast, 8-9-week-old SHR had significantly reduced endothelin-1 in the urine and outer and inner medulla, but not in the cortex or serum compared with those of WKY controls. Furthermore, inner medullary collecting duct cells from 8-9-week-old SHR, either acutely isolated or cultured, released less endothelin-1 than did those from WKY rats. Finally, the level of endothelin-1 messenger RNA was only reduced in the inner medulla and in inner medullary collecting duct cells from 8-9-week-old SHR. In summary, renal medullary, and in particular terminal collecting duct, endothelin-1 production is reduced in SHR only after the development of hypertension. Such decreases in inner medullary collecting duct endothelin-1 production may contribute to the hypertensive state in SHR. and causes a natriuresis and diuresis. 4 These renal actions of ET-1, however, clearly do not cause the same biological responses. For instance, ET-1-induced vasoconstriction reduces glomerular filtration rate, thereby reducing sodium and water excretion, 2 and ET-1 directly inhibits sodium and water reabsorption by the collecting duct. 5 -6 The reasons for this apparent lack of coordinate effects of ET-1 are unknown; however, it probably reflects the independent actions of locally produced ET-1. At least two such locally acting systems exist for ET-1 in the kidney. The first, that of endothelial cell-derived ET-1 modulation of vascular smooth muscle tone, may play a role in the pathogenesis

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Section: Discussioncontrasting

confidence: 99%

Alterations in renal endothelin-1 production in the spontaneously hypertensive rat.

1992

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“…It is also possible that rhuTNF induced not only NO, but compounds with vasoconstrictor properties as well. TNF has been reported to release endothelin-1, a potent vasoconstrictor, from bovine aortic, renal artery and glomerular capillary endothelial cells (46) and has been shown to increase plasma ET-1 and ET-3 after intravenous infusion in the rat (47). The symmetric reduction in CBF to all regions studied suggests either a uniform effect on cellular demand or a direct effect on cerebral vasculature.…”

Section: Discussionmentioning

confidence: 92%

Effect of recombinant human tumor necrosis factor-alpha on cerebral oxygen uptake, cerebrospinal fluid lactate, and cerebral blood flow in the rabbit: role of nitric oxide.

Tureen

1995

J. Clin. Invest.

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Among the important pathophysiologic alterations in the brain in bacterial meningitis are abnormalities of cerebral circulation and metabolism; however, the precise mechanisms by which these disturbances occur are not completely delineated. It has been recently recognized that cytokines are produced by tissues in the central nervous system in meningitis and play a critical role in the host inflammatory response. Because these mediators are involved in circulatory and metabolic disturbances in other tissues in sepsis, we investigated the role of tumor necrosis factor-alpha in the central nervous system in a rabbit model. We found that injection of recombinant human TNF into the cisterna magna in the rabbit led to an acute reduction in cerebral oxygen uptake and a more prolonged reduction in cerebral blood flow. This was accompanied by an increase in intracranial pressure and an increase in cerebrospinal fluid lactate. Reduction in oxygen uptake and increases in intracranial pressure and CSF lactate were blocked by pretreatment with L-NAME, an inhibitor of nitric oxide synthase. Reduction in cerebral blood flow was not affected by L-NAME treatment and was due to increased cerebrovascular resistance and reduced oxygen demand. These results suggest that TNF may be a critical mediator of changes in cerebral circulation and metabolism and that some of these changes occur via the nitric oxide pathway. (J. Clin. Invest. 1995.

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“…[31][32][33] The plasma level of ET-1 increases in several pathophysiological conditions, and it is 2-3 times higher than the normal level in essential hypertension of humans. 6 The plasma concentration of ET-1 increased to 4-7 times the control level in a rat model of acute myocardial infarction, 10 in patients on the day of onset of acute myocardial infarction (3.8±1.7 pg/ml), 33 and in patients with acute myocardial infarction with heart failure (1.97±0.69 -4.54±1.17 pg/ml).…”

Section: Sub-threshold and Threshold Concentration Of Et-1mentioning

confidence: 99%

Effects of Low Doses of Endothelin-1 on Basal Vascular Tone and Autoregulatory Vasodilation in Canine Coronary Microcirculation in Vivo

et al. 1999

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ndothelin (ET)-1 is an endothelium-derived peptide that has a potent vasoconstrictor effect on a variety of vascular beds including the coronary microcirculation. [1][2][3][4] The plasma concentration of the peptide is increased in cardiovascular diseases such as essential hypertension, 5,6 vasospastic angina, 7 acute myocardial infarction, 8 and congestive heart failure. 9 Pretreatment with a monoclonal antibody against endothelin decreases the size of myocardial infarction in rat hearts. 10 The present authors 11 and other groups 12,13 have reported that the opening of ATP-sensitive potassium channels has a crucial role in the dilation of coronary resistance vessels during ischemia, hypoxemia, reactive hyperemia and autoregulation. We have also reported that pertussis toxin (PTX)-sensitive G protein mediates autoregulation and ischemic dilation in the canine coronary microcirculation. 14 On the other hand, ET-1 has been reported to block ATPsensitive potassium channels in cultured smooth muscle cells of the porcine coronary artery. 15 ET-1 also reversibly inhibits ATP-sensitive potassium channels of rat cardiac myocytes via an effect on PTX-sensitive G protein coupled to ET receptors. 16 Therefore, it is possible that a threshold concentration of ET-1 increases the vulnerability of hearts Japanese Circulation Journal Vol.63, August 1999 to myocardial ischemia by increasing the basal tone of coronary vessels or by attenuating the physiological responses such as autoregulation during the reduction in perfusion pressure. Accordingly, we assessed the effect of low doses of ET-1 on the vascular tone and on the physiological responses of coronary microvessels during a reduction in the coronary perfusion pressure. Methods General PreparationTwenty-four small mongrel dogs of either sex, weighing 5.8-9.9 kg, were premedicated with ketamine (10 mg/kg, im) and then anesthetized with an intravenous injection of -chloralose (60 mg/kg, Wako Chemicals). Additional doses, when necessary, were given to maintain anesthesia. The animals were intubated and mechanically ventilated (Model NSH-34RH, Harvard Apparatus, South Natic, MS, USA) at an end expiratory pressure of 3-5 cm H2O. Metabolic acidosis during the experiments was prevented by intravenous infusion of sodium bicarbonate. Arterial blood gases were maintained within the physiological range by adjusting the rate and volume of a ventilator and/or by using oxygen-enriched air. Body temperature was maintained at 37-38°C by means of a homeo-thermic blanket system. A catheter was introduced into the right external jugular vein for the infusion of drugs and fluid. Aortic pressure was measured at the aortic root with a catheter passed through the right carotid artery and Jpn Circ J 1999; 63: 617 -623 (Received April 15, 1999; accepted May 17, 1999 The plasma level of endothelin-1 (ET-1) increases in several cardiovascular disorders. The present study examined whether threshold doses of ET-1 affect vascular tone and autoregulatory vasodilation during a reduction in perfusion p...

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Modulation of Circulating Endothelin Levels in Hypertension and Endotoxemia in Rats

Cited by 63 publications

References 0 publications

Alterations in renal endothelin-1 production in the spontaneously hypertensive rat.

Alterations in renal endothelin-1 production in the spontaneously hypertensive rat.

Effect of recombinant human tumor necrosis factor-alpha on cerebral oxygen uptake, cerebrospinal fluid lactate, and cerebral blood flow in the rabbit: role of nitric oxide.

Effects of Low Doses of Endothelin-1 on Basal Vascular Tone and Autoregulatory Vasodilation in Canine Coronary Microcirculation in Vivo

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