RESUMO
The selective [alpha 2] -adrenoceptor agonist UK-14304 produces a small vasoconstrictor response in the rat isolated carotid artery. The purpose of the work presented here was to investigate whether stimuli that produce submaximal contraction would potentiate responses to UK-14304. Male Wistar rats were killed by overdose with pentobarbitone sodium, after which the left and right common carotid arteries were removed. The rings of arteries 3-4 mm in length were cut from each vessel and then mounted in 10 mL isolated organ bath, bathed in Krebs maintained at 37°C and gassed with 95% 02 plus 5% CO[2] The preparations were allowed to equilibrate for an hour. Cumulative concentration-response curves [CCRC] were constructed in a cumulative manner by increasing the concentration of the agonists in half-log increments. When antagonists were used, the preparations were incubated at least for 45 minutes with the drugs prior to the onset of a second CCRC. Angiotensin II [All] and other contracting factors were added approximately 10-15 min prior to the onset of CCRC to an agonist. After inducing tone with low concentrations of the thromboxane A[2] mimetic agent U-46619 [1nM], 5HT [0.5-1 [micro] M] and phenylephrine [10 [micro] M], exposure of the preparation to UK-14304 resulted in concentration dependent contractions to this agonist. The sensitivity and maximum response of the preparation to UK-14304 were not changed. Inducing tone with AII [0.01 [micro] M] produced a significant leftward shift in the CCRC to UK-14304 [p<0.05]. Thus submaximal contraction with AII [0.01 [micro] M],increased responses significantly, but inducing tone with phenylephrine, U-46619 and 5HT had no effect on responses to UK-14304. The [alpha] -adrenoceptor antagonists prazosin and rauwolscine were examined to see whether UK-14304's main action in the presence of All remained via [alpha 1]. The potentiated responses were prazosin sensitive and rauwolscine resistant, indicating an increasing effect mediated by [alpha 1] -adrenoceptotrs