scholarly journals Mechanisms Underlying Vascular Endothelial Growth Factor Receptor Inhibition–Induced Hypertension

Hypertension ◽  
2021 ◽  
Vol 77 (5) ◽  
pp. 1591-1599
Author(s):  
Kaisa M. Mäki-Petäjä ◽  
Adam McGeoch ◽  
Lucy L. Yang ◽  
Annette Hubsch ◽  
Carmel M. McEniery ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Blood Flow ◽  
Vascular Resistance ◽  
Forearm Blood Flow ◽  
Acetylcholinesterase Activity ◽  
Vascular Endothelial ◽  
Peripheral Vascular ◽  
Induced Hypertension ◽  
Endothelial Growth Factor ◽  
Microvascular Rarefaction

Drugs targeting the VEGF (vascular endothelial growth factor) signaling pathway are approved for several malignancies. Unfortunately, VEGF inhibitors lead to hypertension in 30% to 80% patients. Reduced nitric oxide synthase activity, microvascular rarefaction, and increased vascular resistance have been proposed as potential mechanisms. We aimed to assess these mechanisms in patients receiving the VEGF inhibitor, pazopanib, for cancer. Twenty-seven normotensive patients with advanced solid malignancies received pazopanib 800 mg od. Endothelial function was assessed using forearm plethysmography with intraarterial infusions of acetylcholine. Detailed hemodynamic measurements were taken. Density and diameter of the conjunctival and episcleral microvasculature were evaluated using hemoglobin video imaging. Measurements were taken at baseline, 2, and 12 weeks after initiation of pazopanib or earlier if patients became hypertensive. By the end of the trial, systolic blood pressure increased by 12 mm Hg (95% CI, 4–19 mm Hg; P =0.003), diastolic by 10 mm Hg (95% CI, 5–15 mm Hg; P <0.001), and peripheral vascular resistance by 888 dynes×s/cm 5 (95% CI, 616–1168 dynes×s/cm 5 ; P <0.001). Forearm blood flow improved: Ratio of acetylcholine response at end of trial/baseline was 2.8 (95% CI, 1.84–4.25; P <0.001). Microvascular density in the sclera was reduced by −15.5% (95% CI, −25.7% to −5.3%; P =0.003) and diameter by −2.09 µm (95% CI, −3.95 to −0.19 µm; P =0.03). A post hoc colorimetric assay revealed that pazopanib inhibited acetylcholinesterase activity by −56% (95% CI, −62% to −52%; P <0.001). Unexpectedly, pazopanib led to an increase in acetylcholine-mediated forearm blood flow response, likely due to the inhibition of acetylcholinesterase activity. Pazopanib increased peripheral vascular resistance and reduced microvascular density and diameter, suggesting that microvascular rarefaction could be one of the key mechanisms behind VEGF inhibition–induced hypertension. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01392352.

scholarly journals Female sexual dysfunction in systemic sclerosis: The role of endothelial growth factor and endostatin

2018 ◽  
Vol 4 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Antonietta Gigante ◽  
Luca Navarini ◽  
Domenico Margiotta ◽  
Biagio Barbano ◽  
Antonella Afeltra ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Blood Flow ◽  
Systemic Sclerosis ◽  
Growth Factor ◽  
Sexual Dysfunction ◽  
Resistive Index ◽  
Serum Levels ◽  
Vascular Endothelial ◽  
Healthy Controls ◽  
Endothelial Growth Factor

Introduction: Since female sexual dysfunction in systemic sclerosis women is multifactorial, we can assume that vascular damage may play a role in pathogenesis. The aim of the study was to evaluate the clitoral blood flow, by Echo color Doppler, and to correlate it whit serum levels of vascular endothelial growth factor and endostatin. Methods: A total of 15 systemic sclerosis women and 10 healthy controls matched for sex and age were enrolled in this study. Serum VEGF165 and endostatin levels were determined in systemic sclerosis patients by commercial enzyme-linked immunosorbent assay kit. Clitoral blood flow was measured by Doppler indices of clitoral artery: pulsatile index, resistive index, and systolic/diastolic ratio were measured. Sexual dysfunction was assessed by Female Sexual Function Index. Results: Vascular endothelial growth factor (pg/mL) and endostatin (ng/mL) median values were significantly higher in systemic sclerosis women than healthy controls. Resistive index and systolic/diastolic ratio median values were significantly higher in systemic sclerosis women than healthy controls. Negative correlation exists between serum levels of vascular endothelial growth factor and resistive index (r = −0.55, p < 0.05). Positive correlation was observed between serum levels of endostatin and resistive index (r = 0.70, p < 0.01) and systolic/diastolic ratio (r = 0.77, p < 0.01). Discussion: We can suppose that clitoral blood flow in systemic sclerosis women is reduced not only for macro- and microvascular damage but also for impaired angiogenesis.

scholarly journals Vasodilation secondary to exposure to galvanic currents

2019 ◽  
Vol 02 (02) ◽  
pp. 107-107 ◽  
Author(s):  
Margalef R. ◽  
Minaya Muñoz F. ◽  
Valera Garrido F. ◽  
Santafe MM
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Blood Flow ◽  
Growth Factor ◽  
Inflammatory Reaction ◽  
Vascular Endothelial ◽  
Male Mice ◽  
Galvanic Current ◽  
Vasoactive Substances ◽  
Endothelial Growth Factor ◽  
Control Image

Abstract Background The action of galvanic currents (GC) includes the generation of vasoactive substances such as, for example the vascular endothelial growth factor (VEGF) and its receptor, VEGFR-2. Aim To evaluate modifications in blood flow by action of the galvanic current. Material and Methods The experiments have been performed in Swiss male mice (45-50 days old). The experiments were performed at controlled temperature and light settings. The hypodermis of the skin in the cranial area was used. The procedures were as follows: 1) A portion of skin was sectioned and lifted to obtain a control image; 2) the needle (Physio Invasiva 0.30 × 40mm) was placed over the surface of the skull and covered with skin; 3) treatment was applied using 3 mA, during 3 seconds and three applications (Physio Invasiva Prim); 4) the skin was immediately lifted once again and 3h later to obtain experimental images. In the case of the controls, process 1-4 was repeated, however without applying current. The images were binarized (Digimizer 4.6.1. MedCalc Software) and the area occupied by the vessels of the same surface for each image. Results In mice treated using the GC protocol 3mA, 3 seconds and 3 applications, an increase of 38.53% ± 0.006 was obtained immediately after the application of the GC. However, at three hours, this variation disappears (% of variation: 4.03 ± 0.01), recovering control values. In the control experiments there was no modification. Conclusions Galvanic currents provoke an immediate and transitory vasodilation in mid to small caliber vessels. An immediate and transitory vasodilation has two consequences: the arrival of cells responsible for the inflammatory reaction is accelerated (an essential and necessary step for the regeneration of tissues) and lavage of nociceptive substances is facilitated, which supports an analgesic effect.

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