Vascular biology of angiotensin and the impact of physical activity

Rush, James W. E.; Aultman, Crystal D.
February 2008
Applied Physiology, Nutrition & Metabolism;Feb2008, Vol. 33 Issue 1, p162
Academic Journal
The renin-angiotensin system (RAS) is important for regulating blood pressure and extracellular fluid. The concept of the RAS has recently evolved from a classical systemic endocrine system to an appreciation of local RASs functioning in a paracrine manner, including in the vascular wall. Angiotensin II (AII), the main effector of the RAS, is a potent vasoconstrictor formed by the action of angiotensin-converting enzyme (ACE). ACE is multifunctional and also destroys the endogenous vasodilator bradykinin. A recently discovered novel ACE2 enzyme is responsible for forming a vasodilatory compound, angiotensin 1-7, from AII. Thus, the actions of ACE and ACE2 are antagonistic. Tissue actions of AII are mediated by specific receptors, AT1 and AT2, with AT1 mediating the classical actions. AT1-stimulated vasoconstricton occurs via phospholipase-D-mediated second messenger generation directly, and indirectly via the coupling of AT1 to the prooxidant enzyme NADPH oxidase. Since the vascular NADPH oxidase is a major source of vascular reactive oxygen species generation and is responsible for the breakdown of the vasodilator nitric oxide (NO), there is another potential link between RAS and regulation of vasodilatory pathways. AT2 signaling is antagonistic to AT1 signaling, and results in bradykinin and NO formation. Chronic AII signaling induces vascular dysfunction, whereas pharmacological management of the RAS can not only control blood pressure, but also correct endothelial dysfunction in hypertensives. Exercise training can also improve endothelial function in hypertensives, raising the question of whether there is a potential role for RAS in mediating the vascular effects of exercise training. Recent studies have demonstrated reductions in the expression of NADPH oxidase components in the vascular wall in response to exercise training, thus tempering one of the main cellular effectors of AII, and this is associated with reduced vascular ROS production and enhanced NO bioavailability. Importantly, it has now been demonstrated in human arteries that exercise training also tempers vascular AT1 receptor expression and AII-induced vasoconstriction, while enhancing endothelium-dependent dilation. The signals responsible for these chronic adaptations are not clearly understood, and may include changes in RAS components prompted by acute exercise. ACE genotype may have an effect on physical activity levels and on the cardiovascular responses to exercise training, and the II genotype (compared with ID and DD) is associated with the largest endothelium-dependent dilations in athletes compared with those in sedentary individuals. Thus, the tissue location of the RAS, the complement of ACE/ACE2, the receptor expression of AT1/AT2, and the ACE genotype are all variables that could impact the vascular responses to exercise training, but the responses of most of these variables to regular exercise training and the mechanisms responsible have not been systematically studied.


Related Articles

  • Bradykinin causes selective efferent arteriolar dilation during angiotensin I converting enzyme inhibition. Kon, Valentina; Fogo, Agnes; Ichikawa, Iekuni; Hellings, Samuel E.; Bills, Teresa // Kidney International;Sep1993, Vol. 44 Issue 3, p545 

    We studied the effects of interruption of the renin-angiotensin system (RAS) in rats that were volume depleted by water deprivation for 48 hours (AWD) with/without furosemide (AWD + F), a condition known to activate RAS. Following baseline rnicropuncture, AWD rats (N = 6) were treated with a...

  • The Two fACEs of the Tissue Renin-Angiotensin Systems: Implication in Cardiovascular Diseases. Lazartigues, Eric; Feng, Yumei; Lavoie, Julie L. // Current Pharmaceutical Design;Apr2007, Vol. 13 Issue 12, p1231 

    The implication of the renin-angiotensin system (RAS) in the regulation of the cardiovascular system has been well known for many years. Accordingly, many pharmaceutical inhibitors have been developed to treat several pathologies, like hypertension and heart failure, and angiotensin converting...

  • SECTION 2: CARDIOVASCULAR SYSTEM.  // MPR - Pharmacist's Edition;Spring2010, Vol. 4 Issue 1, p3 

    The article provides information on the classes of antihypertensive drugs including thiazides, angiotensin converting enzyme (ACE) inhibitors and direct renin inhibitors. It states that the hypotensive effects of thiazides is related to arteriolar vasodilatation and its effect is achieved at a...

  • Prils, sartans and nones. Mann, Stewart // New Zealand Doctor;5/4/2005, p29 

    Focuses on the use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blocking agents (ARB). Blockade of ACE inhibtors to the breakdown of vasodilator bradykinin; Reported side effects of ARB; Overview of the renin-angiotensin-aldosterone system. INSET: Key points.

  • Effect of Angiotensin Blockade and Converting Enzyme Inhibition on Reno vascular Hypertension: Comparison Between Unilateral and Bilateral Renal Artery Stenosis. Takabatake, Toshikazu; Ohta, Hiromichi; Yamamoto, Yoshiharu; Yoh-ichi Ishida; Hara, Hiromoto; Ushiogi, Yasuyuki; Nakamura, Saburo; Hattori, Nobu // Angiology;Jun1987, Vol. 38 Issue 6, p434 

    The response to angiotensin II analog infusion during sodium deletion and the effects of a one-month captopril treatment were compared between 15 renovascular hypertensive patients with unilateral and 6 with bilateral renal artery stenosis. Plasma renin activity, its response to sodium...

  • Impact of renin-angiotensin-aldosterone system gene variants on the severity of hypertension in patients with newly diagnosed hypertension. Tiago, Armindo D.; Badenhorst, Danelle; Nkeh, Benedicta; Candy, Geoffrey P.; Brooksbank, Richard; Sareli, Pinhas; Libhaber, Elena; Samani, Nilesh J.; Woodiwiss, Angela J.; Norton, Gavin R. // American Journal of Hypertension;Dec2003, Vol. 16 Issue 12, p1006 

    : BackgroundThe severity of hypertension has prognostic significance. Previous studies have assessed the relationship between renin-angiotensin-aldosterone system (RAAS) genotype and the severity of hypertension in either treated patients or those who have only recently discontinued treatment.:...

  • Local induction of angiotensin-converting enzyme in the kidney as a mechanism of progressive renal diseases. Vío, Carlos P.; Jeanneret, Valerie A. // Kidney International Supplement;Oct2003, Issue 86, p57 

    Local induction of angiotensin-converting enzyme as a mechanism contributing to progressive renal disease. Angiotensin Converting Enzyme (ACE) or Kininase II has a pivotal role determining the local activity of the renin angiotensin and kallikrein kinin systems. Angiotensin II (Ang II), a main...

  • Coronary perfuse pressure is associated with angiotensin-converting enzyme (ACE) in female and with ACE2 activity in male SHR. Bissoli, N.; Dalpiaz, P. L.; Figueiredo, S. G.; Lamas, A.; Caliman, I. F.; Medeiros, A.; Andrade, T.; Alves, M.; Carmona, A. K.; Gonçalves, W.; Moysés, M. // Proceedings of the Physiological Society;2013, p435P 

    The renin-angiotensin system (RAS) plays an important role in the pathophysiology of cardiovascular disease (CVD). ACE (angiotensin-converting enzyme) 2 degrades Ang (angiotensin) II, the main effector of the classic RAS, and generates Ang-(1-7). Thus, ACE2 plays a crucial role in the RAS...

  • Update on the angiotensin converting enzyme 2-angiotensin (1—7)-Mas receptor axis: fetal programing, sex differences, and intracellular pathways. Chappell, Mark C.; Marshall, Allyson C.; Alzayadneh, Ebaa M.; Shaltout, Hossam A.; Diz, Debra I. // Frontiers in Endocrinology;Jan2014, Vol. 5, p1 

    The renin-angiotensin-system (RAS) constitutes an important hormonal system in the physiological regulation of blood pressure. Indeed, dysregulation of the RAS may lead to the development of cardiovascular pathologies including kidney injury. Moreover, the blockade of this system by the...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics