Braylin induces a potent vasorelaxation, involving distinct mechanisms in superior mesenteric and iliac arteries of rats.

Arterial hypertension is a risk factor for various cardiovascular and renal diseases, representing a major public health challenge. Although a wide range of treatment options are available for blood pressure control, many hypertensive individuals remain with uncontrolled hypertension. Thus, the search for new substances with antihypertensive potential becomes necessary. Coumarins, a group of polyphenolic compounds derived from plants, have attracted intense interest due to their diverse pharmacological properties, like potent antihypertensive activities. Braylin (6-methoxyseselin) is a coumarin identified in the Zanthoxylum tingoassuiba species, described as a phosphodiesterase-4 (PDE4) inhibitor. Although different coumarin compounds have been described as potent antihypertensive agents, the activity of braylin on the cardiovascular system has yet to be investigated. To investigate the vasorelaxation properties of braylin and its possible mechanisms of action, we performed in vitro studies using superior mesenteric arteries and the iliac arteries isolated from rats. In this study, we demonstrated, for the first time, that braylin induces potent vasorelaxation, involving distinct mechanisms from two different arteries, isolated from rats. A possible inhibition of phosphodiesterase, altering the cyclic adenosine monophosphate (cAMP)/cAMP-dependent protein kinase (PKA) pathway, may be correlated with the biological action of braylin in the mesenteric vessel, while in the iliac artery, the biological action of braylin may be correlated with increase of cyclic guanosine monophosphate (cGMP), followed by BKCa, Kir, and Kv channel activation. Together, these results provide evidence that braylin can represent a potential therapeutic use in preventing and treating cardiovascular diseases.

Metástase de seminoma em região orbital em cão - relato de caso / Metastatic seminoma in the orbital region in a dog - case report

O seminoma é uma neoformação testicular originária de células germinativas de ocorrência comum em cães, com maior prevalência em animais senis. Em geral, o comportamento biológico do seminoma canino é benigno. Relata-se neste trabalho um caso de seminoma com metástase em região orbital em um cão com 14 anos de idade. O animal foi atendido com queixa de aumento de volume em órbita esquerda, com posterior detecção de nódulo testicular. A punção aspirativa por agulha fina da massa orbital sugeriu tratar-se de linfoma de alto grau, contudo o diagnóstico definitivo de seminoma difuso foi estabelecido pela avaliação histopatológica, a qual revelou tratar-se de neoplasia maligna pouco diferenciada, sendo o diagnóstico de seminoma difuso confirmado pelo exame imunoistoquímico. Relatos de seminomas metastáticos em cães são incomuns. Objetivou-se com este trabalho relatar um caso de seminoma anaplásico difuso em cão cujo foco principal de metástase ocorreu em região orbital, além de descrever e discutir as dificuldades diagnósticas encontradas.(AU)

Seminoma is a testicular neoformation originating from germ cells, commonly occurring in dogs. With higher prevalence in senile animals, the biological behavior of canine seminomas generally benign. This case reports seminoma with mestastasis in the orbital region in a 14-year-old dog. The animal was treated with a complaint of increased volume in the left orbit, and later a nodule in the testicle was discovered. Fine-needle aspiration of the orbit mass initially indicated a high-grade lymphoma. The definitive diagnosis of diffused seminoma was established by histopathological examination, resulting in poorly differentiated malignant neoplasia. Finally, the diagnosis was confirmed through immunohistochemistry, being the result compatible with diffused seminoma. Metastatic seminomas reported in dogs are quite uncommon. In this work we report a case of diffused anaplastic seminoma in dogs, where the main focus of metastasis was observed in the orbital region, and we also describe and discuss the difficulties encountered in the diagnostic.(AU)

NO production and potassium channels activation induced by Crotalus durissus cascavella underlie mesenteric artery relaxation.

Animal toxins are natural resources for pharmacological studies. The venom of Crotalus durissus cascavella (C.d. cascavella) may be a source in the bio-prospecting of new anti-hypertensive agents. The aim of this study was to investigate vascular effects of the venom of C.d. cascavella in normotensive rats. Studies were performed using isolated mesenteric artery segments and aortic endothelial cells. The cumulative administration of the venom of C.d. cascavella (0.001-30 µg/mL) on phenylephrine (Phe; 10 µM) pre-contracted rings induced a concentration-dependent vasorelaxation in the presence of vascular endothelium (Emax = 47.9 ± 5.0% n = 8), and its effect was almost abolished in the absence of endothelium (Emax = 5.8± 2.4% n = 5 (∗∗∗p < 0.001)). Tissue viability was maintained as there was no difference in the contractile capacity of rings before and after the administration of venom. The vasorelaxant effect of the venom was also abolished when arteries were pre-contracted with potassium chloride (KCl; 80 mM) (Emax = 6.4± 0.9% n = 5, ∗∗∗p < 0.001). When assessing the participation of endothelium-derived relaxing factors, it was noted that non-selective COX inhibition with indomethacin (10 µM) caused a significant reduction in the vasorelaxant effect of C.d. cascavella (*p < 0.05). When investigating the participation of NO released by endothelium, there was a significant reduction of the vasorelaxant effect of venom in rings treated with L-NAME (100 µM; Emax = 17.5± 2.2% n = 6; **p < 0.01). Similar results were noted in the presence of ODQ (10 µM), an inhibitor of soluble guanylyl cyclase (Emax = 11.2± 3.5%, n = 6) and PTIO (100 µM), a stable radical scavenger for nitric oxide (Emax = 10.77± 3.6%, n = 6). Moreover, the venom induced the release of NO by isolated aortic endothelial cells through amperometric studies. When assessing the participation of K+ channels on the vasodilatory response of the venom, tyrode solution with 20 mM of KCl caused a significant reduction in the relaxation response (p < 0.001) (Emax = 21.3 ± 8%, n = 7), as did inhibitor of delayed rectifier K+ channels (4-amynopiridine 1 mM; Emax = 9.5 ± 1.3, %, n = 5, ***p < 0.001), and vasorelaxation was almost abolished in the presence of Iberiotoxin (IbTx 100 nM). Therefore, these results suggest that the venom of C.d. cascavella induces vasorelaxation in superior mesenteric artery rings of normotensive rats in an endothelium-dependent manner. Specifically, the venom stimulates the generation of endothelium-derived relaxing factors, especially NO, and activates vascular smooth muscle hyperpolarization through K+ channels. These data illustrate that C.d. cascavella is a source of bioactive molecules and therefore has therapeutic potential in the treatment of cardiovascular diseases such as hypertension.

Evidences of antihypertensive potential of extract from Solanum capsicoides All. in spontaneously hypertensive rats.

BACKGROUND: Solanum capsicoides All. is morphologically similar to Solanum sisymbriifolium Lam. which is used in folk medicine in South America for antihypertensive and diuretics purposes. This similarity has led to species identification errors, which therefore may result in errors by patients. PURPOSE: To evaluate the antihypertensive and diuretics potential of the methanol extract from Solanum capsicoides All. (MeOH-Sc), in vitro and in vivo, in spontaneously hypertensive rats (SHR). METHODS: Initial experiments were performed in rat mesenteric artery to evaluate the in vitro vascular effect of MeOH-Sc and its fractions, in addition to the mechanisms involved during the observed effect. Mean arterial pressure (MAP) and heart rate (HR) were recorded in non-anesthetised hypertensive and normotensive rats. In another set of experiments, MeOH-Sc was administered for 21 consecutive days. Daily body weight measurements were conducted and MAP, HR and urinary volume were measured every 5 days. The mesenteric artery from treated animals was tested for phenylephrine and sodium nitroprussiate (SNP) sensitivity. RESULTS: Initially, MeOH-Sc and fractions relaxed phenylephrine-induced contractions in mesenteric artery rings. The vasorelaxant effect was not changed in the presence of a blocker of eNOS (L-NAME) in rings with an intact endothelium. In denuded-endothelium rings, the vasorelaxant response was significantly reduced in the presence of a cAMP inhibitor (SQ 22536 10 µM) in SHR but not in Wistar Kyoto rats (WKY). However, in the presence of a cGMP inhibitor (ODQ 10 µM), a curve shift to the right was observed in WKY animals, but not in SHR. Intravenous bolus injections of MeOH-Sc into non-anesthetised SHR and WKY, induced hypotension that was associated with an increase in HR. A significant antihypertensive effect was observed in animals that received MeOH-Sc orally for 21 days, which also prevented the development of cardiac hypertrophy. Urine volume from animals treated with MeOH-Sc significantly increased. Finally, MeOH-Sc induced beneficial changes in vascular responsiveness. CONCLUSION: MeOH-Sc has a potential antihypertensive effect in SHR.