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Atrial natriuretic peptide ameliorates hypoxic pulmonary vasoconstriction without influencing systemic circulation

100%

Hohne C., Drzimalla M., Krebs M. O., Boemke W., Kaczmarczyk G.

Journal of Physiology and Pharmacology

2003

tom 54

nr 4

Hypoxic pulmonary vasoconstriction (HPV) is encountered during ascent to high altitude. Atrial natriuretic peptide (ANP) could be an option to treat HPV because of its natriuretic, diuretic, and vasodilatory properties. Data on effects of ANP on pulmonary and systemic circulation during HVP are conflicting, partly owing to anesthesia, surgical stress or uncontrolled dietary conditions. Therefore, ten conscious, chronically tracheotomized dogs were studied under standardized dietary conditions. The dogs were trained to breathe spontaneously at a ventilator circuit. Protocol: 30min of normoxia [inspiratory oxygen fraction (FiO2)=0.21] were followed by 30min of hypoxia without ANP infusion (Hypoxia I, FiO2=0.1). While maintaining hypoxia an intravenous infusion of atrial natriuretic peptide was started with 50ng·kg body wt-1·min-1 for 30min (Hypoxia+ANP1=low dose), followed by 1000ng·kg body wt-1·min-1 for 30min (Hypoxia+ANP2=high dose). Thereafter, ANP infusion was stopped and hypoxia maintained for a final 30min (Hypoxia II). Compared to normoxia, mean pulmonary arterial pressure (MPAP) (16±0.7 vs. 26±1.3mmHg) and pulmonary vascular resistance (PVR) (448±28 vs. 764±89dyn·s-1·cm-5) increased during Hypoxia I and decreased during Hypoxia+ANP 1 (MPAP 20±1mmHg, PVR 542±55dyn·s-1·cm-5) (P<0.05). The higher dose of ANP did not further decrease MPAP or PVR, but started to have a tendency to decrease mean arterial pressure and cardiac output. We conclude that low dose ANP is able to reduce HPV without affecting systemic circulation during acute hypoxia.

Nifedipine inhibits the hypoxia-induced decrease in plasma renin activity in conscious dogs

100%

Hohne C., Arntz E., Krebs M. O., Boemke W., Kaczmarczyk G.

Journal of Physiology and Pharmacology

2003

tom 54

nr 2

Acute hypoxia induces a decrease in plasma renin activity (PRA), mediated, e.g., by an increase in adenosine concentration, calcium channel activity, or inhibition of ATP-sensitive potassium channels. The decrease in PRA results in a decrease in angiotensin II (AngII) and plasma aldosterone concentration (PAC). This study investigates whether these hypoxia-induced mechanisms can be inhibited by the L-type voltage-dependent calcium channel antagonist nifedipine. Eight conscious, chronically tracheotomized dogs received a low sodium diet (0.5 mmol Na·kg body wt-1·day-1). The dogs were studied twice in randomized order, either with nifedipine infusion (1.5 µg·kg body wt-1·min-1, Nifedipine) or without (Control). The dogs were breathing spontaneously: first hour, normoxia [inspiratory oxygen fraction (FiO2)=0.21]; second and third hour hypoxia (FiO2=0.1). In Controls, PRA (6.8±0.8 vs. 3.0±0.5 ngAngI·ml-1·min-1), AngII (13.3±1.9 vs. 7.3±1.9 pg/ml), and PAC (316±50 vs. 69±12 pg/ml) decreased during hypoxia (P<0.05). In Nifedipine experiments, PRA (6.5±0.9 vs. 10.5±2.4 ngAngI·ml-1·min-1) and AngII (14±1.1 vs. 18±3.9 pg/ml) increased during hypoxia, whereas the decrease in PAC (292±81 vs. 153±41 pg/ml) was blunted (P<0.05). These results foster the idea that the hypoxia-induced decrease in PRA involves L-type calcium channel activity.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

2 Boemke W.

2 Hohne C.

2 Kaczmarczyk G.

2 Krebs M. O.

1 Arntz E.

1 Drzimalla M.

2 2003

Wyniki wyszukiwania

Atrial natriuretic peptide ameliorates hypoxic pulmonary vasoconstriction without influencing systemic circulation

Nifedipine inhibits the hypoxia-induced decrease in plasma renin activity in conscious dogs