1. Experiments were undertaken to determine if prejunctional α 1 -adrenoceptors are involved in autoinhibitory regulation of transmitter noradrenaline release in rat atria. 2. The noradrenergic transmitter stores in rat isolated atria were radiolabeled with [ 3 H]noradrenaline and transmitter release was deduced from the efflux of the radiolabel evoked by field stimulation of the atrial intramural sympathetic nerves. 3. Phentolamine (3 μmol/l) and prazosin (0.1 and 3 μmol/l) enhanced the release of radiolabel evoked by stimulation with trains of 4, 8 and 16 pulses, whereas idazoxan (10 μmol/l) enhanced release evoked by stimulation with 8 and 16 pulses. Idazoxan and prazosin were about equieffective in enhancing the evoked release but phentolamine produced much greater enhancement than either idazoxan or prazosin. 4. Combination of idazoxan (10 μmol/l) and prazosin enhanced the stimulation-evoked release with 4, 8 and 16 pulses to the same extent as phentolamine (3 μmol/l). 5. The selective α 1 -adrenoceptor agonist methoxamine (10 μmol/l) inhibited stimulation-evoked release and this effect was blocked by the α 1 -adrenoceptor antagonist prazosin (0.1 μmol/l). 6. The findings indicate that α 1 -adrenoceptors may contribute to autoinhibitory feedback regulation of transmitter release in rat atria.
1. Rats implanted with osmotic minipumps delivering adrenaline intraperitoneally at the rate of 2.9 nmol/h had significantly higher systolic and diastolic pressures from days 2 to 6 after implantation than sham-operated control rats. 2. Concomitant treatment with metoprolol tartrate (2.5 mg/kg, intraperitoneally, twice daily) prevented the elevation in blood pressure induced by adrenaline from osmotic minipumps. Such metoprolol treatment did not affect the blood pressure of control rats. 3. Noradrenaline administered intraperitoneally from osmotic minipumps at the rate of 2.9 nmol/h had no significant effect on blood pressure over a 6-day period of observation. 4. Tachyphylaxis developed to the acute pressor responses to intermittent intravenous infusions of adrenaline in doses of 0.78 μg (4.24 nmol) every 10 min, but after 14 days of such treatment systolic and diastolic blood pressures were significantly greater than in control rats. 5. It is suggested that the increase in blood pressure produced by chronic treatment with adrenaline is due to the uptake and accumulation of adrenaline in noradrenergic nerve terminals, from which it is subsequently released as a cotransmitter that mediates a positive feedback loop on, transmission by acting on prejunctional β-adrenoceptors.
1. Exchangeable body sodium was measured in deoxycorticosterone acetate (DOCA) -salt-treated rats by whole body γ-counting after equilibration with a 22 Na isotope. 2. The blood pressure of DOCA-salt-treated rats is positively correlated with their exchangeable body sodium. 3. After pithing, the heart rate is significantly lower in DOCA-salt-treated than in control rats: in conscious DOCA-salt-treated rats the heart rate is also lower than in control rats but the difference was not statistically significant. 4. Cardiac and vascular responses to sympathetic stimulation are positively correlated with exchangeable body sodium in pithed rats, but there is no correlation between either cardiac or vascular responses to noradrenaline injections and exchangeable sodium. 5. Pressor responses to sympathetic stimulation in pithed DOCA-salt-treated rats are potentiated less by cocaine than are responses of untreated control rats. 6. It is suggested that sodium retention in mildly hypertensive rats specifically enhances responses to sympathetic stimulation by increasing the availability of the sympathetic transmitter.