Increased Angiotensin II Contraction of the Uterine Artery at Early Gestation in a Transgenic Model of Hypertensive Pregnancy Is Reduced by Inhibition of Endocannabinoid Hydrolysis
| Autor: | Victor M Pulgar, Liliya M. Yamaleyeva, K. Bridget Brosnihan, Michael Bader, Carolynne McGee, Allyn C. Howlett, Jasmina Varagic, Ralf Dechend |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Cannabinoid receptor Polyunsaturated Alkamides Blood Pressure Arachidonic Acids Article Amidohydrolases Glycerides Rats Sprague-Dawley chemistry.chemical_compound Piperidines Pregnancy Fatty acid amide hydrolase Internal medicine Internal Medicine medicine Animals Humans Benzodioxoles JZL184 Angiotensin II Hydrolysis Hypertension Pregnancy-Induced Anandamide URB597 Endocannabinoid system Rats Monoacylglycerol lipase Disease Models Animal Uterine Artery Endocrinology chemistry Vasoconstriction Benzamides cardiovascular system Monoglycerides Pregnancy Animal lipids (amino acids peptides and proteins) Female Carbamates Rats Transgenic Endocannabinoids |
| Zdroj: | Hypertension. 64:619-625 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.114.03633 |
| Popis: | Increased vascular sensitivity to angiotensin II (Ang II) is a marker of a hypertensive human pregnancy. Recent evidence of interactions between the renin–angiotensin system and the endocannabinoid system suggests that anandamide and 2-arachidonoylglycerol may modulate Ang II contraction. We hypothesized that these interactions may contribute to the enhanced vascular responses in hypertensive pregnancy. We studied Ang II contraction in isolated uterine artery (UA) at early gestation in a rat model that mimics many features of preeclampsia, the transgenic human angiotensinogen×human renin (TgA), and control Sprague–Dawley rats. We determined the role of the cannabinoid receptor 1 by blockade with SR171416A, and the contribution of anandamide and 2-arachidonoylglycerol degradation to Ang II contraction by inhibiting their hydrolyzing enzyme fatty acid amide hydrolase (with URB597) or monoacylglycerol lipase (with JZL184), respectively. TgA UA showed increased maximal contraction and sensitivity to Ang II that was inhibited by indomethacin. Fatty acid amide hydrolase blockade decreased Ang II MAX in Sprague–Dawley UA, and decreased both Ang II MAX and sensitivity in TgA UA. Monoacylglycerol lipase blockade had no effect on Sprague–Dawley UA and decreased Ang II MAX and sensitivity in TgA UA. Blockade of the cannabinoid receptor 1 in TgA UA had no effect. Immunolocalization of fatty acid amide hydrolase and monoacylglycerol lipase showed a similar pattern between groups; fatty acid amide hydrolase predominantly localized in endothelium and monoacylglycerol lipase in smooth muscle cells. We demonstrated an increased Ang II contraction in TgA UA before initiation of the hypertensive phenotype. Anandamide and 2-arachidonoylglycerol reduced Ang II contraction in a cannabinoid receptor 1–independent manner. These renin–angiotensin system-endocannabinoid system interactions may contribute to the enhanced vascular reactivity in early stages of hypertensive pregnancy. |
| Databáze: | OpenAIRE |
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