No abstract

Serotonin (5-hydroxytryptamine; 5-HT) inhibits the rat cardioaccelerator sympathetic outflow by 5-HT receptors. Because chronic blockade of sympatho-excitatory 5-HT receptors is beneficial in several cardiovascular pathologies, this study investigated whether sarpogrelate (a 5-HT receptor antagonist) alters the pharmacological profile of the above sympatho-inhibition. Rats were pretreated for 2 weeks with sarpogrelate in drinking water (30 mg/kg per day; sarpogrelate-treated group) or equivalent volumes of drinking water (control group). Animals were pithed and prepared for spinal stimulation (C-T) of the cardioaccelerator sympathetic outflow or for intravenous (i.v.) bolus injections of noradrenaline. Both procedures produced tachycardic responses remaining unaltered after saline. Continuous i.v. infusions of 5-HT induced a cardiac sympatho-inhibition that was mimicked by the 5-HT receptor agonists 5-carboxamidotryptamine (5-CT; 5-HT), CP 93,129 (5-HT), or PNU 142633 (5-HT), but not by indorenate (5-HT) in both groups; whereas LY344864 (5-HT) mimicked 5-HT only in sarpogrelate-treated rats. In sarpogrelate-treated animals, i.v. GR 127935 (310 μg/kg; 5-HT receptor antagonist) attenuated 5-CT-induced sympatho-inhibition and abolished LY344864-induced sympatho-inhibition; while GR 127935 plus SB 699551 (1 mg/kg; 5-HT receptor antagonist) abolished 5-CT-induced inhibition. These results confirm the cardiac sympatho-inhibitory role of 5-HT, 5-HT, and 5-HT receptors in both groups; nevertheless, sarpogrelate treatment specifically unmasked a cardiac sympatho-inhibition mediated by 5-HT receptors.

No abstract

No abstract

No abstract

Our results suggest that HEVe induces relaxation through an endothelium-independent pathway, involving blockade of Ca(2+) channels, and this effect could be related to the presence of valepotriates.

The sensory nervous system controls cardiovascular homeostasis via capsaicin-sensitive neurons that release calcitonin gene-related peptide (CGRP), which subsequently activates CGRP receptors. How this perivascular CGRPergic discharge is modulated, nevertheless, remains unclear. In pithed rats, systemic vasodilation induced by CGRPergic discharge stimulation results in diastolic blood pressure (BP) decrements that are inhibited by the dopamine D 2 -like receptor agonist quinpirole. Since this inhibition is mediated by raclopride-or haloperidol-sensitive D 2 -like receptors (comprising the D 2 , D 3 , and D 4 subtypes), the present study pharmacologically investigated the specific contribution of these subtypes to the modulation of the systemic CGRPergic vasodilation, using highly specific antagonists. To that end, 55 male Wistar rats were pithed for thoracic (T 9 −T 12 ) spinal stimulation of the perivascular CGRPergic discharge. The resulting frequency-dependent decrements in diastolic BP were inhibited by quinpirole, and this sensory-inhibition was (a) unchanged after i.v. injections of the antagonists L-741,626 (D 2 ) or L-745,870 (D 4 ) and (b) completely blocked by SB-277011-A (D 3 ). Accordingly, we suggest the main role of the D 3 receptor subtypes in the inhibition by quinpirole of the neurogenic CGRPergic systemic vasodilation. These findings contribute to a better understanding of the dopaminergic modulation of the rat perivascular CGRPergic discharge producing systemic vasodilation.

The phenanthrenes gymnopusin (1), fimbriol A (2), and erianthridin (3) from Maxillaria densa were found to induce significant relaxant effects in a concentration-dependent and endothelium-independent manner on aortic rings precontracted with norepinephrine (NE, 0.1 μM) and KCl (80 mM). Compound 1 was the most active and also inhibited the cumulative concentration-response contraction of NE or CaCl(2). Contractions induced by FPL 64176, an agonist of L-type voltage-dependent calcium channels, were blocked by 1. The potassium channel blockers glibenclamide and TEA (tetraethylammonium) reduced the relaxations induced by 1. Nevertheless, the effect of 1 was not modified by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a specific soluble guanylate cyclase inhibitor. The functional results obtained suggest that 1 induces relaxation through an endothelium-independent pathway by the control of cationic channels (calcium channel blockade and potassium channel opening) in the myogenic response of rat aortic rings.