Abstract P242: The Role Of Kappa Opioid Receptors In The Development Of Hypertension And Kidney Injury In Sprague-Dawley Rats

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Daria Golosova ◽  
Adrian Zietara ◽  
Ruslan Bohovyk ◽  
Vladislav Levchenko ◽  
Alexander Staruschenko
Keyword(s):  
Blood Pressure ◽  
Sprague Dawley ◽  
Glomerular Injury ◽  
Kappa Opioid ◽  
Injury Score ◽  
Calcium Response ◽  
Blood Pressure Elevation ◽  
Isolated Glomeruli ◽  
Pressure Elevation ◽  
Sd Rats

The extensive use of opioid-based pain management strongly correlates with poor cardiovascular and cardiorenal outcomes. Our recent studies suggest that treatment with kappa opioid receptor (KOR) agonist BRL 52537 leads to the progression of chronic kidney disease (CKD) and aggravation of salt-sensitive hypertension. We hypothesize that stimulation of KORs leads to blood pressure elevation, albuminuria, and kidney damage in healthy Sprague-Dawley (SD) rats. To characterize the effect of the KOR agonist BRL 52537 on the development of blood pressure and kidney function in vivo , SD rats were treated with a daily i.v. bolus infusion of BRL 52537 or a corresponding vehicle. To test the contribution of KOR stimulation on calcium homeostasis in podocytes, BRL 52537 was used on freshly isolated glomeruli from SD rats. Single-channel analysis was applied to assess the effect of KORs stimulation on TRPC6 channel activity in the human immortalized podocytes. Chronic treatment with BRL 52537 leads to increased mean arterial pressure (88±1 vs 101±4 mmHg, vehicle vs treated, p<0.05), podocyte basal calcium (90±12 vs 216±16 a.u., vehicle vs treated, p<0.05), and GFB impairment in SD rats which is reflected by a transient increase in albumin excretion (Alb/cre ratio 0.35±0.1 vs 0.72±0.2, vehicle vs treated, p<0.05). Cumulative probability distribution analysis of the glomerular injury score revealed a rightward shift toward a high glomerular injury score in the group treated with BRL 52537 (p<0.05). Angiotensin II level was higher in a BRL-treated group (156±17 vs 232±59 pmol, vehicle vs treated, p=0.065); however, it did not reach a statistical difference. Acute application of BRL 52537 resulted in sustained calcium response (0.23±0.01 a.u., Fluo4/FuraRed, maximum calcium response) in freshly isolated glomeruli from SD rats. Furthermore, patch-clamp experiments in human immortalized podocytes (cell-attached configuration) revealed that BRL 52537 activated TRPC6 channels. Taken together, these data support the hypothesis that administration of opioids in SD rats leads to activation of the KOR/TRPC6 pathway, which in turn led to glomerular filtration barrier impairment, increased glomerular damage, and blood pressure elevation.

scholarly journals 20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension

2013 ◽  
Vol 305 (5) ◽  
pp. F753-F763 ◽  
Author(s):  
Yan Ding ◽  
Cheng-Chia Wu ◽  
Victor Garcia ◽  
Irina Dimitrova ◽  
Adam Weidenhammer ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Dienoic Acid ◽  
Arachidonic Acid Metabolite ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Blood Pressure Elevation ◽  
Pressure Elevation ◽  
Media Thickness ◽  
Microvascular Remodeling ◽  
The Media

20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 (Cyp)-derived arachidonic acid metabolite that has been shown to increase smooth muscle contractions and proliferation, stimulate endothelial dysfunction and activation, and promote hypertension. We examined if 20-HETE contributes to microvascular remodeling in hypertension. In Sprague-Dawley rats, administration of the 20-HETE biosynthesis inhibitor HET0016 or the 20-HETE antagonist N-20-hydroxyeicosa-6( Z),15( Z)-dienoic acid (20-HEDE) prevented 5α-dihydrotestosterone (DHT)-induced increases in blood pressure as well as abrogated DHT-induced increases in the media-to-lumen ratio (M/L), media thickness, and collagen IV deposition in renal interlobar arteries. Reserpine prevented blood pressure elevation in DHT-treated rats but did not affect microvascular remodeling (M/L, media thickness, and collagen deposition); under these conditions, treatment with the 20-HETE antagonist attenuated microvascular remodeling, suggesting that 20-HETE contributes to DHT-induced vascular remodeling independent of blood pressure elevation. In Cyp4a14−/− mice, which display androgen-driven and 20-HETE-dependent hypertension, treatment with the 20-HETE antagonist abolished remodeling of renal resistance arteries measured as media thickness (24 ± 1 vs. 15 ± 1 μm) and M/L (0.29 ± 0.03 vs. 0.17 ± 0.01). Moreover, in Cyp4a12 transgenic mice in which the expression of Cyp4a12–20-HETE synthase is driven by a tetracycline-sensitive promoter, treatment with doxycycline resulted in blood pressure elevation (140 ± 4 vs. 92 ± 5 mmHg) and a significant increase in remodeling of renal resistance arteries (media thickness: 23 ± 1 vs. 16 ± 1 μm; M/L: 0.39 ± 0.04 vs. 0.23 ± 0.02); these increases were abrogated by cotreatment with 20-HEDE. This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels.

Day- and night-time blood pressure elevation in children with higher grades of renal scarring

2003 ◽  
Vol 142 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Ludwig Patzer ◽  
Tomas Seeman ◽  
Carmen Luck ◽  
Elke Wühl ◽  
Jan Janda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Scarring ◽  
Night Time ◽  
Blood Pressure Elevation ◽  
Pressure Elevation

scholarly journals A useful exercise test for detecting leg malperfusion due to aortic dissection

2021 ◽  
Author(s):  
Baku Takahashi ◽  
Keiji Kamohara
Keyword(s):  
Blood Pressure ◽  
Aortic Dissection ◽  
Exercise Test ◽  
Index Test ◽  
Ankle Brachial Pressure Index ◽  
Blood Pressure Elevation ◽  
Pressure Index ◽  
Pressure Elevation ◽  
Key Factor ◽  
Medical Examinations

We herein report a case of leg malperfusion caused by dynamic obstruction after aortic dissection diagnosed by the exercise ankle brachial pressure index test that could not be diagnosed solely by examining the symptoms and investigations at rest. This case suggests that exercise can be a key factor in the diagnosis of this complication. Furthermore, blood pressure elevation can be an exacerbating factor in dynamic obstruction. We recommend conducting an aggressive evaluation of the symptoms and medical examinations not only at rest but also under stress.

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