Hypothalamic and Plasmatic Angiotensin Metabolism in L-NAME Treated Rats

Segarra, Ana Belén; Ramirez, Mariamar Gutierrez; Villarejo, Ana Belén; Banegas, Inmaculada; Vives, Francisco; Gasparo, Marc de; Alba, F; Cobo, Justo; Prieto, Isabel

doi:10.1055/s-0029-1243600

Cited by 5 publications

(14 citation statements)

References 11 publications

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“…L -NAME significantly increased SBP in WKY and SHR as previously reported [4,21]. However, propranolol at the dose used did not modify SBP either in hypertensive animals as previously reported [13] or in WKY rats (fig.…”

Section: Discussionsupporting

confidence: 88%

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Brain, Heart and Kidney Correlate for the Control of Blood Pressure and Water Balance: Role of Angiotensinases

Prieto¹,

Villarejo²,

Segarra³

et al. 2014

Neuroendocrinology

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The renin-angiotensin system (RAS) plays a major role in the control of blood pressure (BP) and water balance by coordinating brain, heart and kidney functions, connected with each other by hormonal and neural mechanisms through the autonomic nervous system (ANS). RAS function may be monitored by the study of the enzymes (angiotensinases) involved in the metabolism of its active peptides. In order to study the relationship between the brain-heart-kidney axis and the control of BP and water balance, we analyzed the correlation of angiotensinase activities, assayed as arylamidase activities, between hypothalamus, left ventricle, renal cortex and renal medulla, collected from Wistar-Kyoto and spontaneously hypertensive rats, treated or not treated with L-NAME [N(G)-nitro-L-arginine methyl ester]. This compound not only inhibits the formation of nitric oxide but also disrupts the normal function of the ANS activating the sympathetic nervous system (SNS) to increase BP. In addition, to assess the influence of the SNS, we studied the effect of its blockade by treatment of both strains with propranolol. The present results support the notion that RAS function of the brain-heart-kidney axis, as reflected by the activities of angiotensinases, is reciprocally connected by afferent and efferent mechanisms between these locations, presumably through the ANS. These results reveal new aspects of neuroendocrine regulation possibly involving the ANS.

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Section: Discussionsupporting

confidence: 88%

“…Compared with control animals, SBP increased significantly in WKY (p < 0.001) [21] and SHR (p < 0.001) [4] after L -NAME treatment. However, SBP was unaffected after propranolol treatment either in WKY or in SHR [13].…”

Section: Resultsmentioning

confidence: 99%

Brain, Heart and Kidney Correlate for the Control of Blood Pressure and Water Balance: Role of Angiotensinases

Prieto¹,

Villarejo²,

Segarra³

et al. 2014

Neuroendocrinology

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“…1 -5 and in • ▶ Table 1 . Compared with control animals, SBP increased signifi cantly in WKY (p < 0.001) [ 5 ] and SHR (p < 0.001) after L-NAME treatment ( • ▶ Fig. 1 ).…”

mentioning

confidence: 92%

“…The hypothalamic stimulatory eff ect of Ang III on vasopressin release has been clearly demonstrated [ 4 ] . Previous observation of increased blood pressure following inhibition of NO synthesis with L-NAME [N(G)-nitro-L -arginine methyl ester] in normotensive Wistar-Kyoto (WKY) suggested the involvement of hypothalamus Ang III and Ang IV and an increase in plasma vasopressin [ 5 ] . Moreover, a neural connection between the frontal cortex and the cardiovascular system through the autonomic nervous system (ANS) has been suggested in spontaneously hypertensive rats (SHR) that involves RAS, vasopressin and NO [ 3 ] .…”

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confidence: 99%

Relationship of Angiotensinase and Vasopressinase Activities Between Hypothalamus, Heart, and Plasma in L-NAME-Treated WKY and SHR

et al. 2014

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The renin-angiotensin system (RAS), vasopressin, and nitric oxide (NO) interact to regulate blood pressure at central and peripheral level. To improve our understanding of their interaction and their relationship with the hypothalamus and the cardiovascular system, we analyzed angiotensin- and vasopressin-metabolizing activities in hypothalamus (HT), left ventricle (LV), and plasma, collected from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) treated or not with L-NAME [N(G)-nitro-L-arginine methyl ester], which inhibits the formation of NO and over-activates the sympathetic nervous system. Previous observations in WKY suggested higher formation of Ang III and Ang IV in the HT and higher availability of Ang II in plasma after L-NAME treatment. Our current results show higher formation of Ang IV and higher metabolism of vasopressin after treatment with L-NAME in the LV of WKY rats. In SHR treated with L-NAME, there is higher availability of Ang III in the HT leading to higher release of vasopressin together with lower formation of Ang 2-10. In their LV, however, there is an increase of vasopressinase. Interestingly, while the enzymatic activities in the HT and LV of WKY rats and control SHR are poorly correlated, they are well but inversely correlated in the L-NAME treated SHR. On the other hand, no significant correlations between enzymatic activities in HT or LV and plasma were noticed. Our results suggest that eNOS inhibition in SHR induces or enhances an inverse reciprocal interaction between HT and LV involving the RAS and vasopressin, which may be mediated by the autonomic nervous system.

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“…To ensure the complete recovery of activity, the detergent was removed from the medium by adding adsorbent polymeric Biobeads SM-2 (100 mg/mL) (Bio-Rad, Richmond, VA, USA) to the samples and shaking for 2 h at 4 °C [ 18 ] . AP activities were measured fl uorometrically as described elsewhere by using aminoacyl-β-naphthylamides (aaNNap) as substrates [ 19 ] , modifi ed [ 20 ] as follows: 96-well (each one with a volume of 250 μl) black round-bottomed polystyrene untreated microplates were used for enzymatic determinations. 20 μl of each supernatant (from soluble or membrane-bound fraction) were incubated during 30 min for all enzymatic activities at 37 °C with 100 μl of the corresponding substrate solution.…”

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confidence: 99%

Effects of Antihypertensive Drugs on Angiotensinase Activities in the Testis of Spontaneously Hypertensive Rats

et al. 2012

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Sexual dysfunction is a frequent adverse effect during antihypertensive therapy. However, the mechanisms responsible for these effects are not well understood. The renin-angiotensin system has been identified in testis where it may play a role in testicular function and be involved in the detrimental effects of antihypertensive drugs. Therefore, our objective was to compare the influence of captopril and propranolol on plasma testosterone levels and on hydrolyzing angiotensin's enzymes (angiotensinases) in the testis of spontaneously hypertensive rats (SHRs) and in control animals. Twenty-four adult male SHRs were used in this study; eight were treated with captopril in drinking water, 8 with propranolol, and 8 were controls. At the end of the 4 weeks treatment period, systolic blood pressure (SBP) was recorded, blood samples were collected, and the right testis was dissected after perfusion of the rat with saline. The soluble (Sol) and membrane-bound (MB) fractions were obtained after solubilization and ultracentrifugation. Fluorometric measurement of Sol and MB angiotensinase activities were performed using arylamide derivatives as substrates. Testosterone was measured by enzyme immunoassay. SBP decreased after captopril but did not change with propranolol treatment. Whereas captopril did not affect angiotensinase activities, highly significant reductions in Sol and MB angiotensinase activities, particularly glutamyl- and aspartyl-aminopeptidases, were observed after treatment with propranolol. Plasma testosterone decreased in captopril treated rats but propranolol had a greater effect. The present results support a general functional depression of the RAS cascade in the testis of propranolol-treated SHR, which may influence the sexual function of these animals.

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Hypothalamic and Plasmatic Angiotensin Metabolism in L-NAME Treated Rats

Cited by 5 publications

References 11 publications

Brain, Heart and Kidney Correlate for the Control of Blood Pressure and Water Balance: Role of Angiotensinases

Brain, Heart and Kidney Correlate for the Control of Blood Pressure and Water Balance: Role of Angiotensinases

Relationship of Angiotensinase and Vasopressinase Activities Between Hypothalamus, Heart, and Plasma in L-NAME-Treated WKY and SHR

Effects of Antihypertensive Drugs on Angiotensinase Activities in the Testis of Spontaneously Hypertensive Rats

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