Inducible NO synthase (NOS II) was proposed to play an important role in salt resistance of Dahl salt-resistant (SR/Jr) rats. Its chronic inhibition by specific inhibitors was accompanied by blood pressure (BP) elevation in animals subjected to high salt intake. The aim of our study was to evaluate 1) whether such inhibitors affect BP and/or its particular components (sympathetic tone and NO-dependent vasodilation) only under the conditions of high salt intake, and 2) whether similar BP effects are elicited after systemic or intracerebroventricular (icv) application of these inhibitors. Wistar rats fed Altromin diet (0.45 % NaCl) and SR/Jr rats fed either a low-salt (LS, 0.3 % NaCl) or a high-salt (HS, 4 % NaCl) diet were studied. Aminoguanidine (AMG) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) were used as NOS II inhibitors. BP and its responses to acute blockade of renin-angiotensin system (captopril), sympathetic nervous system (pentolinium) and NO synthase (L-NAME) were measured in conscious cannulated rats. There were no significant changes of BP or its components in either Wistar rats or SR/Jr rats subjected to chronic inhibition of NOS II by peroral aminoguanidine administration (50 mg/kg/day for 4 weeks). This was true for SR/Jr rats fed either LS or HS diets. Furthermore, we have studied BP effects of chronic icv administration of both NOS II inhibitors in SR/Jr rats fed HS diet, but we failed to find any BP changes elicited by such treatment. In conclusion, inducible NO synthase does not participate in the resistance of SR/Jr rats to hypertensive effects of excess salt intake.
- MeSH
- chlorid sodný MeSH
- hypertenze * chemicky indukované MeSH
- krevní tlak fyziologie MeSH
- krysa rodu rattus MeSH
- kuchyňská sůl * MeSH
- oxid dusnatý MeSH
- potkani inbrední Dahl MeSH
- potkani Wistar MeSH
- synthasa oxidu dusnatého, typ II MeSH
- synthasa oxidu dusnatého MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- diabetes mellitus 2. typu prevence a kontrola MeSH
- kardiovaskulární nemoci prevence a kontrola MeSH
- kouření škodlivé účinky MeSH
- kuchyňská sůl škodlivé účinky MeSH
- ledviny * fyziologie MeSH
- lidé MeSH
- minerální vody škodlivé účinky MeSH
- nežádoucí účinky léčiv MeSH
- pití alkoholu škodlivé účinky MeSH
- pohybová aktivita MeSH
- zdravá strava MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
- MeSH
- chlorid sodný MeSH
- hypertenze * diagnóza farmakoterapie epidemiologie MeSH
- kuchyňská sůl škodlivé účinky MeSH
- lidé MeSH
- sodík dietní * škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Few studies have investigated the hemodynamic mechanism whereby primary aldosteronism causes hypertension. The traditional view holds that hyperaldosteronism initiates hypertension by amplifying salt-dependent increases in cardiac output (CO) by promoting increases in sodium retention and blood volume. Systemic vascular resistance (SVR) is said to increase only as a secondary consequence of the increased CO and blood pressure. However, mounting evidence indicates that aldosterone can influence multiple pathways regulating vascular tone. We investigated the primary hemodynamic mechanism whereby hyperaldosteronism promotes salt sensitivity and initiation of salt-dependent hypertension. METHODS: In unilaterally nephrectomized male Sprague-Dawley rats given infusions of aldosterone or vehicle, we used chronically implanted arterial pressure probes and Doppler ultrasonic flow probes to continuously monitor changes in mean arterial pressure, CO, and SVR 24 hours/day, 7 days/week in response to increases in salt intake. RESULTS: In vehicle-treated control rats, switching from a low-salt diet to a high-salt diet initiated modest increases in mean arterial pressure by increasing SVR while simultaneously decreasing heart rate and CO. In aldosterone-treated rats compared with control rats, switching from a low-salt diet to a high-salt diet initiated significantly greater increases in mean arterial pressure and SVR and significantly greater decreases in heart rate and CO. CONCLUSIONS: Aldosterone promoted salt sensitivity and initiation of salt-dependent hypertension by amplifying salt-induced increases in SVR while decreasing CO. Increases in CO are not required for the initiation or maintenance of hypertension. These findings challenge the traditional view of the hemodynamic mechanisms that cause hypertension in primary aldosteronism.
- MeSH
- aldosteron MeSH
- cévní rezistence MeSH
- hemodynamika MeSH
- hyperaldosteronismus * komplikace MeSH
- hypertenze * MeSH
- krevní tlak MeSH
- krysa rodu rattus MeSH
- kuchyňská sůl škodlivé účinky MeSH
- minutový srdeční výdej MeSH
- potkani Sprague-Dawley MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The agonists of alpha(2)-adrenergic receptors such as clonidine, rilmenidine or monoxidine are known to lower blood pressure (BP) through a reduction of brain sympathetic outflow but their chronic antihypertensive effects in rats with low-renin or high-renin forms of experimental hypertension were not studied yet. Moreover, there is no comparison of mechanisms underlying BP reduction elicited by chronic peroral (po) or intracerebroventricular (icv) clonidine treatment. Male salt-sensitive Dahl rats fed 4% NaCl diet and Ren-2 transgenic rats were treated with clonidine administered either in the drinking fluid (0.5 mg/kg/day po) or as the infusion into lateral brain ventricle (0.1 mg/kg/day icv) for 4 weeks. Basal BP and the contributions of renin-angiotensin system (captopril 10 mg/kg iv) or sympathetic nervous system (pentolinium 5 mg/kg iv) to BP maintenance were determined in conscious cannulated rats at the end of the study. Both peroral and intracerebroventricular clonidine treatment lowered BP to the same extent in either rat model. However, in both models chronic clonidine treatment reduced sympathetic BP component only in rats treated intracerebroventricularly but not in perorally treated animals. In contrast, peroral clonidine treatment reduced angiotensin II-dependent vasoconstriction in Ren-2 transgenic rats, whereas it lowered residual blood pressure in Dahl rats. In conclusions, our results indicate different mechanisms of antihypertensive action of clonidine when administered centrally or systemically.
- MeSH
- angiotensin II farmakologie MeSH
- antihypertenziva farmakologie MeSH
- chlorid sodný MeSH
- clonidin farmakologie MeSH
- hypertenze * chemicky indukované farmakoterapie MeSH
- hypotenze * MeSH
- krevní tlak MeSH
- krysa rodu rattus MeSH
- kuchyňská sůl MeSH
- potkani inbrední Dahl MeSH
- potkani transgenní MeSH
- renin MeSH
- sympatický nervový systém MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
High-salt diets are a major cause of hypertension and cardiovascular (CV) disease. Many governments are interested in using food salt reduction programs to reduce the risk for salt-induced increases in blood pressure and CV events. It is assumed that reducing the salt concentration of processed foods will substantially reduce mean salt intake in the general population. However, contrary to expectations, reducing the sodium density of nearly all foods consumed in England by 21% had little or no effect on salt intake in the general population. This may be due to the fact that in England, as in other countries including the U.S.A., mean salt intake is already close to the lower normal physiologic limit for mean salt intake of free-living populations. Thus, mechanism-based strategies for preventing salt-induced increases in blood pressure that do not solely depend on reducing salt intake merit attention. It is now recognized that the initiation of salt-induced increases in blood pressure often involves a combination of normal increases in sodium balance, blood volume and cardiac output together with abnormal vascular resistance responses to increased salt intake. Therefore, preventing either the normal increases in sodium balance and cardiac output, or the abnormal vascular resistance responses to salt, can prevent salt-induced increases in blood pressure. Suboptimal nutrient intake is a common cause of the hemodynamic disturbances mediating salt-induced hypertension. Accordingly, efforts to identify and correct the nutrient deficiencies that promote salt sensitivity hold promise for decreasing population risk of salt-induced hypertension without requiring reductions in salt intake.
- MeSH
- chlorid sodný MeSH
- kuchyňská sůl * MeSH
- stravovací zvyklosti * MeSH
- Úřad Spojených států pro potraviny a léky MeSH
- Publikační typ
- práce podpořená grantem MeSH
- úvodníky MeSH
- Geografické názvy
- Spojené státy americké MeSH
- MeSH
- analýza moči * MeSH
- kreatinin MeSH
- lidé MeSH
- sbírání vzorku moči MeSH
- sodík dietní * MeSH
- sodík MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- Aspirin škodlivé účinky terapeutické užití MeSH
- glifloziny terapeutické užití MeSH
- hodnocení rizik MeSH
- hypoglykemika terapeutické užití MeSH
- kuchyňská sůl škodlivé účinky MeSH
- lidé MeSH
- srdeční selhání * farmakoterapie prevence a kontrola MeSH
- zdravá strava MeSH
- zdravý životní styl MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
The important participation of sympathetic nervous system in various forms of experimental hypertension is well known. This is also true for salt hypertension elicited by excess salt intake in Dahl salt-sensitive rats (for review see Zicha et al. 2012). Two recent studies in Dahl rats (Zicha et al. 2019, Puleo et al. 2020) evaluated the hypothesis on the role of beta-adrenergic WNK4-NCC pathway in salt-sensitive hypertension which has been proposed by Mu et al. (2011). Although these studies differed in many experimental details, both of them demonstrated a major importance of alpha1- rather than beta-adrenergic mechanisms for the development of salt hypertension in this rat strain.
- MeSH
- chlorid sodný MeSH
- hypertenze * MeSH
- krysa rodu rattus MeSH
- kuchyňská sůl * MeSH
- potkani inbrední Dahl MeSH
- sympatický nervový systém MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- komentáře MeSH
- úvodníky MeSH
