Mechanisms Underlying the Vascular Actions of Endothelin 1, Angiotensin II and Bradykinin in the Rat Carotid

Abstract

The carotid artery has a pivotal role in the body since it supplies the head and neck with oxygenated blood. Alterations in the functional and structural integrity of these vessels can decrease blood flow to the brain. For this reason, it is important to understand how the carotid artery responds to various stimuli. The organ bath is a traditional experimental set-up that has been used extensively to investigate the (patho)physiology and pharmacology of in vitro tissue preparations including the rat carotid artery. Molecular biology developed from related fields such as biochemistry, genetics and biophysics is now considered an important tool for understanding physiological pathways in a variety of tissues. Several local and systemic factors regulate carotid reactivity, including vaso-active peptides, such as endothelin 1 (ET-1), angiotensin II (Ang II) and bradykinin (BK). These vaso-active peptides play a fundamental role in controlling the functional and structural integrity of the arterial wall and may be important in physiological processes and in pathological mechanisms underlying vascular diseases. In the rat carotid, these peptides induce vasoconstriction or relaxation by the release of endothelium-derived relaxing factors, such as nitric oxide and prostacyclin. Identification of such signal transduction processes is essential for understanding the mechanisms that regulate vascular smooth muscle cell function, both physiologically and pathophysiologically. The present review discusses the mechanisms of action, distribution of ET-1, Ang II and BK and their receptors in the rat carotid. With this purpose, data obtained in functional studies using classical pharmacological approaches as well as data obtained in molecular biology experiments are discussed.

Vascular endothelium – Gatekeeper of vessel health

“…Indeed, with the exception of renin (which cleaves angiotensinogen to form angiotensin I), all components of the RAS are produced in the vasculature. Endothelial cells express angiotensin converting enzyme (ACE), the dipep-tidyl carboxypeptidase that converts angiotensin-1 to the physiologically active angiotensin-II (Ang-II) [191]. Both local and circulating Ang-II exert their activities through the binding to Ang-II type 1 (AT1) or type 2 (AT2) receptors.…”

The Role of Sartans in the Treatment of Stroke and Subarachnoid Hemorrhage: A Narrative Review of Preclinical and Clinical Studies

“…Given that in most clinical centers, antihypertensive agents are discontinued during the period of DCVS, LS, although an antihypertensive drug, may have a role in preventing delayed DCVS after aneurysm rupture given the effects shown in ischemia. Following aSAH, immediate therapy with LS might antagonize the vasoconstrictive AT 2 -1-R without affecting the dilatory AT 2 -2-R effect [132,[144][145][146][147][148][149][150][151]. Furthermore, AT 2 interestingly increases endothelin production in non-cerebral vessels (an increased ET-1 concentration in rat aortas could be inhibited through LS administration [140]) and thus indirectly enhances ET-1-mediated DCVS [123,[152][153][154][155][156].…”

The Roles of Cycloxygenase and Endothelial Derived Hyperpolarizing Factors in Bradykinin-Induced Aortic Relaxation

“…The nonapeptide BK considered as potent vasoactive peptide that is formed in the plasma by cleavage of a high-molecular-weight kininogen. Bradykinin exerts its physiological effects through two G-proteincoupled receptors, termed the B 1 and B 2 receptors (Tirapelli, Bonaventura, Tirapelli, & de Oliveira, 2009). In endothelial cells, BK through Ca 2+ -mediated mechanisms stimulates endothelial nitric oxide synthase (eNOS) and increased production of nitric oxide (NO) and cGMP, that results in vasorelaxation in the vascular bed (Jagdish N Sharma, 2013).…”