Angiotensin II, dopamine and nitric oxide. An asymmetrical neurovisceral interaction between brain and plasma to regulate blood pressure

Figure 1.. The renin-angiotensin aldosterone system. Simplified scheme of the RAAS in which its most active components (peptides and enzymes) stand out in bold with a larger size. In brown, peptides without known biological activity. In red, some of the peptides for which various functions have been described. In green, some of the enzymes responsible for the formation and inactivation of the various angiotensins. The formation of angiotensin II, by the action of ACE on angiotensin I, and its subsequent hydrolysis by aminopeptidase A, leading to the formation of angiotensin III, which will be subsequently inactivated by aminopeptidase M, are important steps especially highlighted in the figure. Angiotensin II is classically considered as the main peptide of the system, target of various therapeutic strategies (inhibiting its formation or blocking its action) for the treatment of hypertension [12]. Angiotensin III is believed to be the main angiotensin in brain, with hypertensive properties. Recent therapeutic strategies against hypertension are aimed at reducing its formation through the use of central inhibitors of aminopeptidase A [12]–[15] From the dynamics of the enzymatic cascade, low…

Figure 2.. Brain dopaminergic system. Simplified representation of the brain dopaminergic system. From the substantia nigra (SN) and ventrotegmental area (VTA) the dopaminergic neurons project unilaterally, without bilateral crossing, toward the cortex (C), limbic system (L) or striatum (ST). This distribution allows to selectively study the consequences of unilateral depletions of dopamine from the left or right hemisphere, offering a valuable tool for the study of the function of brain asymmetry [19].

Figure 3.. Plasma nitric oxide and aminopeptidase activity after left or right lesion. Schematic representation of the consequences of left or right nigrostriatal lesion on plasma levels of nitric oxide (NO) (red arrows) and aminopeptidase A (AP) (blue arrows) in normotensive animals (WKY) and spontaneous hypertensive rats (SHR). (=) indicates that there is no variation compared to control animals. The lesioned hemisphere in the rat brain appears in brown color. Drawings under brains represent blood vessels with sectioned endothelial cells. Gray arrows represent the left or right autonomic innervation of the blood vessels [7].

Figure 4.. Hypothetic Ang III levels after left or right nigrostriatal lesions. Schematic representation of the hypothetical levels of Ang III in the left (red arrows) or right (blue arrows) hemisphere, considering the results obtained for aminopeptidase M activity (high enzymatic activity /low Ang III concentration and vice versa) in groups of WKY or SHR in which the left or right nigrostriatal systems were lesioned [9].