Tachyphylaxis to the vasopressor effects of endothelin in rat aortic rings

Endothelin-1 (ET-1), a potent vasoconstrictor peptide released by endothelial cells, binds with high affinity to surface receptors and is highly resistant to dissociation. We observed tachyphylaxis to the pressor effects of a second application of ET-1 in rat aortic rings and investigated the mechanism of this effect. Developed tension increased progressively with doses of ET-1 ranging from 1 to 500 nM (P < 0.001), and tensions with rechallenge were correspondingly decreased (P < 0.001). In response to 500 nM ET-1, tension increased 1,599 +/- 72 (SE) mg/mg ring wt. Rechallenge with 500 nM ET-1 led to contraction of only 33 +/- 40 mg/mg ring wt. Tachyphylaxis was seen up to 6 h after initial challenge. Pretreatment with nicardipine, lidoflazine, nitroglycerin, and sphingosine did not affect tachyphylaxis. Pretreatment with 500 microM dansylcadaverine (an inhibitor of endothelin internalization) markedly inhibited ET-1-induced contraction and also inhibited tachyphylaxis to ET-1. Further studies with radiolabeled ET-1 suggested that subsequent ET-1 binding is markedly decreased after an initial ET-1 challenge. Dansylcadaverine inhibited ET-1 internalization and also inhibited the decreased binding seen with ET-1 rechallenge. Rat aortic rings demonstrate tachyphylaxis to the pressor effect of a second dose of ET-1. The mechanism appears to be related to binding and subsequent internalization of endothelin-receptor complexes. This effect suggests a possible mechanism for sustained decreases in systemic vascular resistance.

Download Full-text

Suppression of baroreceptor discharge by endothelin at high carotid sinus pressure

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.263.1.r103 ◽

1992 ◽

Vol 263 (1) ◽

pp. R103-R108 ◽

Cited By ~ 11

Author(s):

M. W. Chapleau ◽

G. Hajduczok ◽

F. M. Abboud

Keyword(s):

Endothelial Cells ◽

Arterial Pressure ◽

Carotid Sinus ◽

High Dose ◽

Nerve Activity ◽

Local Exposure ◽

Potent Vasoconstrictor ◽

Alpha Chloralose ◽

Vasoconstrictor Peptide ◽

Sinus Pressure

Endothelin is a potent vasoconstrictor peptide released from endothelial cells capable of producing marked and prolonged increases in arterial pressure. The purpose of this study was to determine whether endothelin alters the sensitivity of arterial baroreceptors. Multifiber baroreceptor activity was recorded from the vascularly isolated, endothelium-denuded carotid sinus in dogs anesthetized with alpha-chloralose. Local exposure of baroreceptors to endothelin at a concentration of 10(-8) M produced vasoconstriction of the carotid sinus as measured with sonomicrometer crystals but did not alter baroreceptor discharge significantly. A higher concentration of endothelin (10(-7) M) markedly suppressed baroreceptor activity, particularly at pressures greater than 100 mmHg (n = 7, P less than 0.05). The magnitude of the decrease in activity was dependent on the duration of exposure to endothelin. Baroreceptor activity measured at carotid pressures of 60, 100, and 200 mmHg averaged 23 +/- 4, 65 +/- 6, and 100 +/- 0% of maximum during control; 38 +/- 12, 61 +/- 9, and 74 +/- 15% after exposure to endothelin (10(-7) M) for 2 min; and 27 +/- 8, 53 +/- 12, and 56 +/- 19% after 12 min, respectively. The suppression of nerve activity with the high dose of endothelin was not accompanied by additional vasoconstriction, suggesting a direct effect of endothelin on nerve endings. We speculate that endothelin released from endothelial cells may act in a paracrine manner to suppress activity of baroreceptors, particularly at high levels of arterial pressure. Such an action would interfere with the buffering capacity of the baroreflex and promote hypertension.

Download Full-text

A novel potent vasoconstrictor peptide produced by vascular endothelial cells

Nature ◽

10.1038/332411a0 ◽

1988 ◽

Vol 332 (6163) ◽

pp. 411-415 ◽

Cited By ~ 7851

Author(s):

Masashi Yanagisawa ◽

Hiroki Kurihara ◽

Sadao Kimura ◽

Yoko Tomobe ◽

Mieko Kobayashi ◽

...

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Potent Vasoconstrictor ◽

Vasoconstrictor Peptide

Download Full-text

Physiologic and hemodynamic changes in patients undergoing open abdominal cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

Journal of International Medical Research ◽

10.1177/0300060520983263 ◽

2021 ◽

Vol 49 (1) ◽

pp. 030006052098326

Author(s):

Myoung Hwa Kim ◽

Young Chul Yoo ◽

Sun Joon Bai ◽

Kang-Young Lee ◽

Nayeon Kim ◽

...

Keyword(s):

Body Temperature ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Intraperitoneal Chemotherapy ◽

Cytoreductive Surgery ◽

Hyperthermic Intraperitoneal Chemotherapy ◽

Resistance Index ◽

Volume Index ◽

Hemodynamic Changes ◽

Arterial Blood

Objective We aimed to determine the physiological and hemodynamic changes in patients who were undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) cytoreductive surgeries. Methods This prospective, observational study enrolled 21 patients who were undergoing elective cytoreductive surgery with HIPEC at our hospital over 2 years. We collected vital signs, hemodynamic parameters including global end-diastolic volume index (GEVI) and extravascular lung water index (ELWI) using the VolumeView™ system, and arterial blood gas analysis from all patients. Data were recorded before skin incision (T1); 30 minutes before HIPEC initiation (T2); 30 (T3), 60 (T4), and 90 (T5) minutes after HIPEC initiation; 30 minutes after HIPEC completion (T6); and 10 minutes before surgery completion (T7). Results Patients showed an increase in body temperature and cardiac index and a decrease in the systemic vascular resistance index. GEDI was 715.4 (T1) to 809.7 (T6), and ELWI was 6.9 (T1) to 7.3 (T5). Conclusions HIPEC increased patients’ body temperature and cardiac output and decreased systemic vascular resistance. Although parameters that were extracted from the VolumeView™ system were within their normal ranges, transpulmonary thermodilution approach is helpful in intraoperative hemodynamic management during open abdominal cytoreductive surgery with HIPEC. Trial registry name: ClinicalTrials.gov Trial registration number: NCT02325648 URL: https://clinicaltrials.gov/ct2/results?cond=NCT02325648&term

Download Full-text

Endothelins activate Na+/H+ exchange in brain capillary endothelial cells via a high affinity endothelin-3 receptor that is not coupled to phospholipase C.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)67686-6 ◽

1991 ◽

Vol 266 (9) ◽

pp. 5925-5928

Author(s):

P Vigne ◽

A Ladoux ◽

C Frelin

Keyword(s):

Endothelial Cells ◽

Phospholipase C ◽

Brain Capillary ◽

High Affinity ◽

Brain Capillary Endothelial Cells ◽

Capillary Endothelial Cells ◽

Endothelin 3

Download Full-text

Empagliflozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular filling pressure in patients with type 2 diabetes: a randomized controlled study

Cardiovascular Diabetology ◽

10.1186/s12933-020-01175-5 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Matthias Rau ◽

Kirsten Thiele ◽

Niels-Ulrik Korbinian Hartmann ◽

Alexander Schuh ◽

Ertunc Altiok ◽

...

Keyword(s):

Cardiac Index ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Resistance Index ◽

Stroke Volume Index ◽

Left Ventricular ◽

Volume Index ◽

Hemodynamic Parameters ◽

Mitral Inflow ◽

Ventricular Filling Pressure

Abstract Background In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial) treatment with the sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin significantly reduced heart failure hospitalization (HHF) in patients with type 2 diabetes mellitus (T2D) and established cardiovascular disease. The early separation of the HHF event curves within the first 3 months of the trial suggest that immediate hemodynamic effects may play a role. However, hitherto no data exist on early effects of SGLT2 inhibitors on hemodynamic parameters and cardiac function. Thus, this study examined early and delayed effects of empagliflozin treatment on hemodynamic parameters including systemic vascular resistance index, cardiac index, and stroke volume index, as well as echocardiographic measures of cardiac function. Methods In this placebo-controlled, randomized, double blind, exploratory study patients with T2D were randomized to empagliflozin 10 mg or placebo for a period of 3 months. Hemodynamic and echocardiographic parameters were assessed after 1 day, 3 days and 3 months of treatment. Results Baseline characteristics were not different in the empagliflozin (n = 22) and placebo (n = 20) group. Empagliflozin led to a significant increase in urinary glucose excretion (baseline: 7.3 ± 22.7 g/24 h; day 1: 48.4 ± 34.7 g/24 h; p < 0.001) as well as urinary volume (1740 ± 601 mL/24 h to 2112 ± 837 mL/24 h; p = 0.011) already after one day compared to placebo. Treatment with empagliflozin had no effect on the primary endpoint of systemic vascular resistance index, nor on cardiac index, stroke volume index or pulse rate at any time point. In addition, echocardiography showed no difference in left ventricular systolic function as assessed by left ventricular ejections fraction and strain analysis. However, empagliflozin significantly improved left ventricular filling pressure as assessed by a reduction of early mitral inflow velocity relative to early diastolic left ventricular relaxation (E/eʹ) which became significant at day 1 of treatment (baseline: 9.2 ± 2.6; day 1: 8.5 ± 2.2; p = 0.005) and remained apparent throughout the study. This was primarily attributable to reduced early mitral inflow velocity E (baseline: 0.8 ± 0.2 m/s; day 1: 0.73 ± 0.2 m/sec; p = 0.003). Conclusions Empagliflozin treatment of patients with T2D has no significant effect on hemodynamic parameters after 1 or 3 days, nor after 3 months, but leads to rapid and sustained significant improvement of diastolic function. Trial registration EudraCT Number: 2016-000172-19; date of registration: 2017-02-20 (clinicaltrialregister.eu)

Download Full-text