Clinical and experimental evidence has shown that
myocardial ischemia activates cardiac spinal afferents that mediate sympathoexcitatory reflex responses. During
myocardial ischemia,
thromboxane A2 (TxA2) is released in large quantities by activated platelets in the coronary circulation of patients with
coronary artery disease. We hypothesized that endogenous TxA2 contributes to sympathoexcitatory reflexes during
myocardial ischemia through stimulation of TxA2/
prostaglandin endoperoxide (
TP) receptors. Regional
myocardial ischemia was induced by occlusion of a diagonal branch of left anterior descending coronary artery of anesthetized cats. Hemodynamic parameters and renal sympathetic nerve activity were recorded after sinoaortic
denervation and bilateral
vagotomy. Regional
myocardial ischemia evoked significant increases in mean blood pressure (122+/-10 vs. 139+/-12 mmHg, before vs.
ischemia), aortic flow (153+/-18 vs. 167+/-20 ml/min), first derivative of left ventricular pressure at 40-mmHg developed pressure (2,736+/-252 vs. 2,926+/-281 mmHg/s), systemic vascular resistance (0.6+/-0.1 vs. 0.9+/-0.12 peripheral resistance units), and renal sympathetic nerve activity (by 22%). The reflex nature of the excitatory responses was confirmed by observing its disappearance after blockade of cardiac nerve transmission with intrapericardial 2%
procaine treatment. Moreover, application of
U-46619 (2.5-10 microg), a TxA2 mimetic, on the heart caused graded increases in mean arterial pressure and renal nerve activity, responses that were abolished 3 min after local blockade of cardiac neural transmission with intrapericardial
procaine.
BM 13,177 (30 mg/kg iv), a selective
TP receptor antagonist, eliminated the reflex responses to
U-46619 and significantly attenuated the excitatory responses during brief (5 min) regional
myocardial ischemia. The sympathoexcitatory reflex responses to
U-46619 were unchanged by blockade of
histamine H1 receptors with
pyrilamine and
serotonin 5-HT3 receptors with
tropisetron, indicating specificity of this
TP receptor agonist. These data indicate that endogenous TxA2 participates in
myocardial ischemia-mediated sympathoexcitatory reflex responses through a
TP receptor mechanism.