Effect of the AT1-Receptor Antagonists Losartan, Irbesartan, and Telmisartan on Angiotensin II-Induced Facilitation of Sympathetic Neurotransmission in the Rat Mesenteric Artery

Q4 · MEDICINE

Article

Author: Nap, Alexander ; Pfaffendorf, Martin ; Mathy, Marie-Jeanne ; van Zwieten, Pieter A. ; Balt, Jippe C.

SUMMARYThe effect of the AT1-receptor antagonists losartan, irbesartan, and telmisartan on angiotensin II (Ang II)-induced facilitation of noradrenergic neurotransmission was investigated in the isolated rat mesenteric artery under isometric conditions. Electrical field stimulation (2, 4, and 8 Hz) caused a frequency-dependent increase of contractile force. At stimulation frequencies of 2, 4, and 8 Hz, Ang 11 (10 nM) increased the stimulation-induced vasoconstrictor responses by a factor 4.8 +/- 0.9, 2.9 +/- 0.7, and 1.3 +/- 0.1, respectively (p < 0.05 compared with control for all frequencies). The enhancement could be concentration-dependently antagonized by losartan (1 nM-1 microM), irbesartan (0.1 nM-0.1 microM), and telmisartan (0.01 nM-0.01 microM). At a stimulation frequency of 2 Hz, the relation between stimulation-induced vasoconstrictor responses (in presence of Ang II 10 nM) and the concentration of the AT1-antagonists used could be described by linear regression. The order of potency concerning sympathoinhibition was telmisartan > irbesartan > losartan (p < 0.05 between linear regression lines). Contractile responses to exogenous noradrenaline were unaltered in the presence of Ang II 10 nM. We conclude that the facilitating effect of Ang II on noradrenergic neurotransmission is mediated by presynaptically located AT1-receptors. Conversely, this facilitating effect can be dose-dependently counteracted by blockade of these receptors. Sympathoinhibitory properties are likely to contribute to the therapeutic effect of AT1-blockers, in particular in conditions in which the sympathetic nervous system is activated, such as congestive heart failure and hypertension.

01 Jan 2000·Biological and Pharmaceutical BulletinQ4 · MEDICINE

Evidence for the AT1 Subtype of the Angiotensin II Receptor in the Rat Submandibular Gland.

Q4 · MEDICINE

Article

Author: Osawa, Masami ; Saito, Kiyoshige ; Matsubara, Shigeru ; Kaizawa, Yasuo ; Sano, Masakazu ; Iwamoto, Keishi ; Murakami, Hajime

We have characterized angiotensin II (Ang II) receptor subtypes on rat submandibular gland membranes using a radioligand binding assay. [3H]Ang II binding to the membrane fractions exhibited both high (Kd =0.08 nm, Bmax =2.19 fmol/mg protein) and low (Kd =4.19 nm, Bmax = 13.7 fmol/mg protein) affinity. Ang 11, Ang III and saralasin completely displaced the [3H]Ang II binding, whereas CV-11974, an AT1 receptor antagonist and PD123319, an AT2 receptor antagonist maximally displaced up to approximately 87 and 13% of the total binding, respectively. [3H]DuP753 binding to the membrane fractions exhibited a single population of binding site with a Kd of 4.22 nM and Bmax of 3.77 pmol/mg protein. Ang II, Ang III and CV-11974 completely displaced the [3H]DuP753 binding with slope factors near unity, but PD123319 did not. These findings suggest that rat submandibular gland membranes contain predominantly the AT1 receptor subtype.

01 Apr 1982·Life SciencesQ3 · MEDICINE

Angiotensin II mediated acth release in rat pituitary cell culture

Q3 · MEDICINE

Article

Author: Anthony Vagnucci ; Douglas Sobel

Anterior pituitaries from normal rats were enzymatically dispersed and placed into monolayer cell culture in order to determine if and how angiotensin II (Ang II) mediates the in vitro release of ACTH and other pituitary hormones. Ang II stimulated ACTH secretion in a time dependent fashion. This release occurred at physiologic concentrations of Ang II and was linearly correlated with the log dose of Ang II. One hour pretreatment of the cells with cycloheximide, a inhibitor of protein synthesis, significantly decreased the cellular ACTH secretory response to Ang II. Ang 11 did not mediate the release of LH nor of ADH, a proposed stimulator of ACTH secretion.

100 Deals associated with ANG-011

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Malabsorption Syndromes	Discovery	US	Anagram Therapeutics, Inc.	06 Nov 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

ANG-011

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation