Pharmacological properties of presynaptic .BETA.-adrenoceptors in guinea-pig pulmonary arteries.

Abstract

Abstract-Pharmacologicalproperties of the facilitatory presynaptic i3-adrenoceptor mechanism were studied in superfused spiral preparations of guinea-pig pulmonary arteries preloaded with 3H norepinephrine. (-) Isoproterenol (0.3 /IM) -induced increases in total 3H efflux per pulse evoked by transmural field stimulation (1, 5, 10 and 20 Hz, 10 V, 2 msec pulse width, 100 pulses and 30 min intervals) were neither dependent on impulse-frequencies nor selective at lower frequencies. Isoproterenol increased 3H efflux at 5 Hz in a concentration-dependent manner (1 nM to 1 itM): pD2 was 7.7. Salbutamol increased 3H efflux in a similar manner to isoproterenol: pD2 was 7.4. Prenalterol at 3 /LM only slightly increased 3H efflux. Tazolol (10 nM to 3 i M) produced no increases. Atenolol (3 iiM) and practolol (3 i M) did not antagonize isoproterenol (0.3 /N)-induced increases in 3H efflux . Butoxamine (3 ;tM) and H 35/25 (3 /N) did antagonize this parameter.

Presynaptic Modulation by Adrenaline of ³H-Noradrenaline Release in Rabbit Ear Artery

“…1). This confirms findings with guinea pig pulmonary artery [23] and rat perfused kidney [24] where adrenaline solely produced an attenuation of the stimulation-evoked transmitter release. On the other hand, exogenously applied adrenaline enhanced the stimulation-evoked 3H overflow in rat portal vein [25], human omental blood vessels [20] and human dig ital arteries [26].…”

“…According to this propo sal, inhibition of presynaptic (^-adrenocep tors should unmask the presence of presyn aptic P2-adrenoceptors, if any. Thus, adrena line enhanced the stimulation-evoked 3H-noradrenaline release in the presence of (a) phenoxybenzamine from rat portal vein [27,28]; (b) phentolamine from guinea-pig pul monary artery [23] and rat perfused kidney [24] , and (c) rauwolscine from human pul monary artery [29]. However, in the present study, adrenaline did not enhance the stimu lation-evoked 3H overflow in the presence of rauwolscine ( fig.…”

Isoproterenol-induced facilitation of norepinephrine release does not primarily involve a local angiotensin II mechanism in guinea pig pulmonary arteries.

“…Spirally cut preparations of the pulmonary arteries from male guinea pig weighing 200 to 250 g were prepared and incubated at 37'C for 60 min with oxygenated Krebs bicarbonate solution containing 0.1 i M 3H norepinephrine (Amersham/Searle) and 100 mg/I ascorbic acid, and then they were mounted vertically between a pair of platinum stimulating electrodes and superfused with Krebs medium at a constant rate of 0.5 ml/ min as described previously (7)(8)(9)(10). The solution, maintained at 37°C, pH 7.2 to 7.4, was bubbled with 5% CO2 in 02.…”

Release of 3H‐Noradrenaline from Rabbit Isolated Ear Artery

“…This is probably due to the fact that at high frequencies, so much of the transmitter is released that the maximum capacity of the modulating negative feed-back system is exceeded and hence plays a quantitatively insignificant role in controlling the release. An enhancement of transmitter release per pulse was also seen with the canine saphenous vein (Saelens & Williams 1983), guinea pig pulmonary artery (Misu et al 1984) and rabbit pulmonary artery (Nedergaard 1988).…”