Calcium channel blockade blunts the renal effects of acute nitric oxide synthase inhibition in healthy humans

Montanari A, Lazzeroni D, Pelà G, Crocamo A, Lytvyn Y, Musiari L, Cabassi A, Cherney DZ. Calcium channel blockade blunts the renal effects of acute nitric oxide synthase inhibition in healthy humans. Am J Physiol Renal Physiol 312: F870–F878, 2017. First published February 8, 2017; doi:10.1152/ajprenal.00568. 2016.—Our aim was to investigate whether blockade of calcium channels (CCs) or angiotensin II type 1 receptors (AT1R) modulates renal responses to nitric oxide synthesis inhibition (NOSI) in humans. Fourteen sodium-replete, healthy volunteers underwent 90-min infusions of 3.0 g·kg1·min1 NG-nitro-L-arginine methyl ester (L-NAME) on 3 occasions, preceded by 3 days of either placebo (PL), 10 mg of manidipine (MANI), or 50 mg of losartan (LOS). At each phase, mean arterial pressure (MAP), glomerular filtration rate (GFR; inulin), renal blood flow (RBF; p-aminohippurate), urinary sodium (UNaV), and 8-isoprostane (U8-iso-PGF2V; an oxidative stress marker) were measured. With PL L -NAME, the following changes were observed: 6% MAP (P 0.005 vs. baseline), 10% GFR, 20% RBF, 49% UNaV (P 0.001), and 120% U8-iso-PGF2V (P 0.01). In contrast, MAP did not increase during LOS L-NAME or MANI L-NAME (P 0.05 vs. baseline), whereas renal changes were the same during LOS L-NAME vs. PL L-NAME (ANOVA, P 0.05). However, during MANI L-NAME, changes vs. baseline in GFR (6%), RBF (12%), and UNaV (34%) were blunted vs. PL L-NAME and LOS L-NAME (P 0.005), and the rise in U8-iso-PGF2V was almost abolished (37%, P 0.05 vs. baseline; P 0.01 vs. PL L-NAME or LOS L-NAME). We conclude that, since MANI blunted L-NAME-induced renal hemodynamic changes, CCs participate in the renal responses to NOSI in healthy, sodium-replete humans independent of changes in MAP and without the apparent contribution of the AT1R. Because the rise in U8-iso-PGF2V was essentially prevented during MANI L-NAME, CC blockade may oppose the renal effects of NOSI in part by counteracting oxidative stress responses to acutely impaired renal NO bioavailability

Effects of "Central Hypervolemia" by water immersion on renin -aldosterone system and ACTH-cortisol axis in haemodialyzed patients

Water immersion up to the neck (WI) results in a central hypervolemia; the increased atrial pressure, evoked by this maneuver, stimulates low pressure receptors (LPR) which exert tonic inhibition on sympathetic activity and suppresses both the renin (PRA)-aldosterone (PA) system and the ACTH-cortisol axis in normal man. In hemodialyzed patients (HP), in whom autonomic neuropathy has been frequently found, PRA and ACTH were not suppressed during WI while plasma cortisol and PA were reduced. Other modulators, like dopamine, are supposed to be involved in regulating cortisol and PA levels in HP

Circulating opioid peptides during water immersion in normal man

Circulating opioid peptides during water immersion in normal man. Coruzzi P, Ravanetti C, Musiari L, Biggi A, Vescovi PP, Novarini A. SourceIstituto di Semeiotica Medica, University of Parma, Italy. Abstract 1. This study was designed to evaluate variations in plasma beta-endorphin, methionine-enkephalin, adrenocorticotropic hormone and serum prolactin in healthy volunteers during head-out water immersion. 2. Water immersion induced an increase in methionine-enkephalin plasma levels, which was associated with a significant fall in mean arterial pressure and heart rate. 3. Conversely, a suppression of plasma beta-endorphin, adrenocorticotropic hormone and serum prolactin was detected during water immersion. 4. We suggest that a dopaminergic inhibitory control mechanism may be involved in regulating circulating levels of beta-endorphin, adrenocorticotropic hormone and prolactin in normal subjects undergoing extracellular fluid volume expansion produced by water immersion

Variabilità della pressione arteriosa in soggetti ipertesi essenziali con e senza sindrome metabolica

Abstract Obiettivi: verificare se al maggior rischio cardiovascolare nella Sindrome Metabolica (SM) associ una elevata variabilità pressoria. Metodi: allo studio hanno partecipato 28 soggetti ipertesi senza SM (20 m, 8 f, età 43.9±1.3, BMI 28.1±.9.) e 30 con SM (21 m, 9 f, età 45.4±2.2, BMI 29.4±.8). L'appartenenza al gruppo SM era definita in base ai criteri NCEP-ATP 111, risultandone tra i due gruppi differenze significative per: circonferenza addomi naie (91.5±1.9 cm vs 103.0±1.5, 0.001), indice HOMAIR (0.001), colesterolo totale, HDL ed LDL (0.02, 0.009, 0.05), trigliceridi e rapporto trigliceridi/HDL(0.001). 20/28 soggetti senza SM e 22/30 con SM erano trattati, senza differenze nella distribuzione dei diversi farmaci. I due gruppi erano sottoposti a monitoraggio pressorio 24 ore, con intervalli di misura di 15 minuti nelle ore diurne (h 7-23) e 20 minuti in quelle notturne. La variabilità della pressione arteriosa e della frequenza cardiaca erano stimate come deviazione • standard dai valori medi delle pressioni sistolica (PAS) e diastolica ( PAD), e della frequenza durante il giorno, la notte e le 24 ore. Risultati: PAS e PAD medie non differivano nei 2 gruppi (PAS 24 h:134.3 ±2.6 mmHg negli SM vs 134.3±3.1; PAS giorno :139.6±2.7 vs137.4±3.2; PAS notte: 118.9±2.7vs 119.0±3.3. PAD 24 h:82.5±1.8 vs83.2±1.9; PAD giorno:86.2±1.9 vs 86.8±1.8; PAD notte 71.9±2.1 vs 71.0±1.6). La deviazione standard della PAS era significativamente più elevata nelle 24 h (17.9±0.8 vs15.2±0.7, p<0.01), di giorno (15.4±0.9 vs 13.2±0.7, p<0.05) e di notte (13.7±1.2 vs 10.3±D.9, p<0.02). La frequenza cardiaca non differiva. tra i due gruppi né come valori medi né come variabilità. Conclusioni: Il presente studio dimostra come in soggetti ipertesi con SM, pur in presenza di valori pressori mediamente sovrapponibili a quelli di un gruppo di controllo composto da pazienti pure ipertesi, ma esenti da SM, la variabilità della PAS sia significativamente più elevata in ogni fase circadiana. Poiché un aumento della variabilità presso ria, specie notturna, é ritenuto un fattore indipendente di rischio cardiovascolare, i nostri rilievi mettono in evidenza un ulteriore elemento potenzialmente aggiuntivo al già elevato rischio associato alla SM