Role of cyclooxygenase-1-mediated prostacyclin synthesis in endothelium-dependent vasoconstrictor activity of porcine interlobular renal arteries

This study aimed to determine whether PGI2 would be evoked by the endogenous endothelial B2 receptor agonist bradykinin (BK) in the porcine interlobular renal artery and, if so, to determine how it would influence the vasomotor reaction, and the specific cyclooxygenase (COX) isoform(s) involved in its synthesis. The production of the PGI2 metabolite 6-keto-PGF1α was analyzed with HPLC-mass spectroscopy, while vasomotor reaction to PGI2 or BK was determined with isometric force measurement. Results showed that BK evoked an increase in the production of 6-keto-PGF1α, which was abolished by endothelial denudation that removed COX-1 expression, or was reduced by COX-1 inhibition. Interestingly, PGI2 evoked a potent contraction, which was prevented by antagonizing thromboxane-prostanoid (TP) receptors and was not enhanced by antagonizing the vasodilator PGI2 (IP) receptors. The IP receptor agonists MRE-269 and iloprost did not induce any relaxation. Moreover, iloprost, which is also a PGI2 analog, caused a contraction, which was sensitive to TP receptor antagonism, but was to a significantly lesser extent than that of PGI2. Indeed, IP receptors were not detected by RT-PCR or Western blotting in the vessel. Following nitric oxide synthase (NOS) inhibition, BK also evoked an endothelium-dependent contraction, which was blocked by TP receptor antagonism. In addition, inhibition of COX-1 (but not COX-2) impeded the vasoconstrictor activity of BK and expedited the relaxation induced by the agonist in NOS-intact vessels. These results demonstrate that in the porcine interlobular renal artery BK evokes endothelial COX-1-mediated PGI2 synthesis, which mainly leads to the activation of TP receptors and a vasoconstrictor response, possibly due to a scarcity of vasodilator activity mediated by IP receptors. Also, our data suggested that the effect of a PGI2 analog on TP receptors could be reduced compared with that of PGI2 due to modified structure as with iloprost.

Central control of sympathetic cardiac augmentation in lower brain stem of the cat

Fifty-three vagotomized cats under chloralose were studied for cardiac augmentation, cardioacceleration, and vasomotor reaction on direct stimulation of the medulla oblongata and via reflex activations. Cardiac augmentation as well as other cardiovascular responses could be induced on stimulation of the dorsal medulla or the central cut end of the sciatic nerves, or on occlusion of the carotid arteries. The augmentation and other responses remained essentially unchanged regardless of the presence or absence of the rostral neural structures, including the hypothalamus. The results confirm and support the concept that a central control mechanism for vasomotor reaction and cardioacceleration as well as augmentation resides in the dorsal region of the lower brain stem.