Use of an indwelling catheter for examining cardiovascular responses to pericardial administration of bradykinin in rat.

OBJECTIVE AND METHODS

Epicardial application of pharmacologic agonists has been used to study nociceptive and reflex responses to agents such as bradykinin. We utilized a model where intrapericardial bradykinin was administered in a closed-chest rat. The procedure allows for reproducible administration of microliter doses of pharmacologic agonists in both conscious and anesthetized animals.

RESULTS

Bradykinin (BK) has been shown to produce sympathoexcitatory reflexes when applied to the heart. BK typically produced a dose-dependent (0.001-10 micrograms) decrease in arterial blood pressure and tachycardia in pentobarbital-anesthetized rats. In contrast, in alpha-chloralose-anesthetized or awake rats, pericardial administration of BK produced a dose-dependent (0.001-10 micrograms) increase in arterial blood pressure and tachycardia. Maximal cardiovascular changes were produced by 1 microgram BK. The maximum change in arterial pressure was +33.6 +/- 9% in awake, +38.9 +/- 6% in chloralose-anesthetized, and -20 +/- 7% in pentobarbital-anesthetized rats. In alpha-chloralose-anesthetized rats, tachyphylaxis to pericardial administration of 1 microgram BK occurred at 5 and 15, but not at 30 min dosing intervals. Administration of the receptor selective B2-antagonist D-Arg,[Hyp3,Thi5,8 D-Phe7]-BK (200 micrograms) or the mixed B2/B1 antagonist [Thi5,8,D-Phe7]-BK (200 micrograms), produced similar attenuation of the pressor and tachycardia responses to BK. Bilateral transection of the cervical vagus nerve, bilateral removal of the stellate ganglion or ganglion blockade (hexamethonium), but not administration of indomethacin, reduced the magnitude of the tachycardia to BK. Only ganglionic blockade significantly reduced the pressor response to BK.

CONCLUSIONS

These results demonstrate that pericardial administration of BK produces a tachycardia and pressor effect in awake and alpha-chloralose-anesthetized rats and a tachycardia and depressor effect in pentobarbital-anesthetized rats. These responses appear to be mediated through activation of BK (presumably B2) receptors on cardiac vagal and sympathetic afferents, and may include a direct action of BK on the heart. This model of pericardial administration of pharmacologic agonists may be useful in studies of cardiac pain and reflex responses.