Objectives: Our main objectives were to investigate the affinity properties of endothelial and muscular α1D -adrenoceptors and to characterize the cross-talk between endothelial α1D -adrenoceptors and β2 -adrenoceptors in rat carotid.
Methods: Relaxation and contraction concentration-response curves for phenylephrine (α1 -adrenergic agonist) were obtained in carotid rings in absence or presence of increasing concentrations of BMY7378 (α1D -adrenergic antagonist), combined or not with increasing concentration of ICI-118,551 (β2 -adrenergic antagonist). Schild analysis was used to estimate the affinity constant from pA2 values of BMY7378.
Key Findings: BMY7378 produced an unsurmountable antagonism on phenylephrine-induced relaxation but a surmountable antagonism on phenylephrine-induced contraction. BMY7378 potency was higher in inhibiting the relaxation than the contraction induced by phenylephrine because the rightward shifts induced by BMY7378 were greater in the relaxation. The apparent pA2 value for BMY7378 in phenylephrine-induced relaxation was greater than in contraction. When combined with ICI-118,551, BMY7378 yielded a surmountable antagonism on phenylephrine-induced relaxation and presented a pA2 value similar to that obtained in phenylephrine-induced contraction.
Conclusions: Endothelial α1D -adrenoceptors, which mediates rat carotid relaxation, present high ligand affinity because of the cross-talk with β2 -adrenoceptors, which explains the higher potency of phenylephrine in inducing relaxation than contraction and the atypical unsurmountable antagonism produced by BMY7378 on phenylephrine-induced relaxation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/jphp.12105 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genetic variation in CCDC93 is associated with elevated central systolic blood pressure, impaired arterial relaxation, and mitochondrial dysfunction.
PLoS Genet
September 2024
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Article Synopsis
- This research focuses on examining genetic associations with central systolic blood pressure (cSBP) in a Chinese population, which has been less studied compared to European ancestries.
- The study identifies novel genetic variants, specifically a variant in the CCDC93 gene, and its significant association with increased cSBP.
- Functional analysis in mice reveals that loss of Ccdc93 leads to higher blood pressure and altered metabolic pathways, indicating its crucial role in blood pressure regulation.
Isoflurane increases the activity of the vascular matrix metalloproteinase-2 in non-pregnant rats and increases the nitric oxide metabolites in pregnancy.
Biosci Rep
June 2024
Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu, Sao Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil.
Surgeries that require general anesthesia occur in 1.5-2% of gestations. Isoflurane is frequently used because of its lower possibility of affecting fetal growth.
View Article and Find Full Text PDFThe antidiabetic drug ipragliflozin induces vasorelaxation of rabbit femoral artery by activating a Kv channel, the SERCA pump, and the PKA signaling pathway.
Eur J Pharmacol
June 2024
Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea. Electronic address:
We explored the vasorelaxant effects of ipragliflozin, a sodium-glucose cotransporter-2 inhibitor, on rabbit femoral arterial rings. Ipragliflozin relaxed phenylephrine-induced pre-contracted rings in a dose-dependent manner. Pre-treatment with the ATP-sensitive K channel inhibitor glibenclamide (10 μM), the inwardly rectifying K channel inhibitor Ba (50 μM), or the Ca-sensitive K channel inhibitor paxilline (10 μM) did not influence the vasorelaxant effect.
View Article and Find Full Text PDFRegulation of vascular angiotensin II type 1 and type 2 receptor and angiotensin-(1-7)/MasR signaling in normal and hypertensive pregnancy.
Biochem Pharmacol
February 2024
Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. Electronic address:
Normal pregnancy (Norm-Preg) is associated with a slight reduction in blood pressure (BP) and decreased BP response to vasoconstrictor stimuli such as angiotensin II (Ang II), although the renin-angiotensin-aldosterone system (RAAS) is upregulated. Preeclampsia (PE) is a complication of pregnancy manifested as hypertension-in-pregnancy (HTN-Preg), and dysregulation of angiotensin biosynthesis and signaling have been implicated. Ang II activates vascular Ang II type-1 receptor (ATR) and Ang II type-2 receptor (ATR), while angiotensin-(1-7) promotes Ang-(1-7)/MasR signaling.
View Article and Find Full Text PDFEndothelium-Independent Vasorelaxant Effects of Sudachitin and Demethoxysudachitin, Polymethoxyflavone from the Peel of Citrus sudachi on Isolated Rat Aorta.
Biol Pharm Bull
November 2023
Laboratory of Functional Food Sciences, Department of Health and Bio-Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University.
Although polymethoxyflavones have been reported to exhibit various pharmacological actions, the effects of polymethoxyflavones sudachitin and demethoxysudachitin from the peel of Citrus sudachi on the cardiovascular system have not been clarified. This study investigated the mechanisms of vasorelaxation induced by sudachitin and demethoxysudachitin in rat aorta. Both compounds inhibited phenylephrine-induced contractions in a concentration-dependent manner.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!