Intrinsic vasomotricity and adrenergic effects in a model of isolated rabbit eye

Título da Revista: Acta Ophthalmologica ScandinavicaPurpose: We aimed to investigate the responsiveness of the ocular arteries to adrenergic drugs in a model of perfused isolated rabbit eye. Methods: Rabbit external ophthalmic arteries (n = 15) in a head-mounted preparation were cannulated and the retinal and uveal vasculature perfused at a constant flow with warmed tyrode. The three-way polypropylene catheter was further connected to a pressure transducer and intraluminal pressure was taken as a measure of vascular resistance. Effects of intra-arterial injections of phenylephrine (group A, n = 5), prazosin (group B, n = 5) and phentolamine (group C, n = 5) on the recorded pressure were obtained. Student’s paired-t test and one-way analysis of variance were used for statistical analysis (p < 0.05). Results: Intrinsic vasomotricity was observed in all preparations prior to any drug administration. Phenylephrine produced an increase in total vascular resistance. Intrinsic vasomotricity became more evident, showing a lower frequency but higher amplitude of oscillations. Evoked vasomotor responses with phenylephrine (250 lg ⁄ ml) were inhibited by intra-arterial administration of the selective a1-adrenergic antagonist, prazosin (0.5 mg⁄ ml), as well as the non-selective a-adrenergic antagonist phentolamine (6 mg⁄ ml). Conclusions: Rabbit external ophthalmic arteries showed spontaneous contractions under constant perfusion. Phenylephrine elicited a vasoconstrictor response that was inhibited by adrenergic antagonists. In addition, the intrinsic vasomotricity was enhanced by phenylephrine and blocked by adrenergic antagonists. These results show that under in vitro perfusion the territory presents similar responses to adrenergic drugs to those observed in in vivo models and also provides evidence of myogenic autoregulatory properties in the rabbit ophthalmic artery and ⁄ or choroidCIISA (Centro de Investigação Interdisciplinar em Sanidade Animal

Angiotensin-(1-7) and angiotensin-(1-9): function in cardiac and vascular remodeling

The renin angiotensin system (RAS) is integral to cardiovascular physiology, however, dysregulation of this system largely contributes to the pathophysiology of cardiovascular disease (CVD). It is well established that angiotensin II (Ang II), the main effector of the RAS, engages the angiotensin type 1 receptor and promotes cell growth, proliferation, migration and oxidative stress, all processes which contribute to remodeling of the heart and vasculature, ultimately leading to the development and progression of various CVDs including heart failure and atherosclerosis. The counter-regulatory axis of the RAS, which is centered on the actions of angiotensin converting enzyme 2 (ACE2) and the resultant production of angiotensin-(1-7) (Ang-(1-7) from Ang II, antagonizes the actions of Ang II via the receptor Mas, thereby providing a protective role in CVD. More recently, another ACE2 metabolite, Ang-(1-9), has been reported to be a biologically active peptide within the counter-regulatory axis of the RAS. This review will discuss the role of the counter-regulatory RAS peptides, Ang-(1-7) and Ang-(1-9) in the cardiovascular system, with a focus on their effects in remodeling of the heart and vasculature

Development of CALUX bioassay-based systems as instruments to detect hormones and contaminants

α-Adrenoceptors mediate contractile responses in equine digital veins (EDVs) and arteries. Vascular smooth muscle

Relative contribution of Rho kinase and protein kinase C to myogenic tone in rat cerebral arteries in hypertension

Arterial smooth muscle constriction in response to pressure, i.e., myogenic tone, may involve calcium-dependent and calcium-sensitization mechanisms. Calcium sensitization in vascular smooth muscle is regulated by kinases such as PKC and Rho kinase, and activity of these kinases is known to be altered in cardiovascular disorders. In the present study, we evaluated the relative contribution of PKC and Rho kinase to myogenic tone in cerebral arteries in hypertension. Myogenic tone and arterial wall calcium in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were measured simultaneously, and the effect of PKC and Rho kinase inhibitors on myogenic tone was evaluated. SHR arteries showed significantly greater myogenic tone than WKY arteries. Pressure/wall tension-arterial wall calcium curves showed a hyperbolic relation in WKY rats, but the curves for SHR arteries were parabolic. Myogenic tone was decreased by the Rho kinase inhibitors Y-27632 and HA-1077, with a significantly greater effect in SHR than in WKY arteries. Reduction in myogenic tone produced by the PKC inhibitor bisindolylmaleimide I in WKY and SHR arteries was significantly less than that produced by Rho kinase inhibition. The pressure-dependent increase in myogenic tone was significantly decreased by Y-27632, and the decrease was markedly greater than that produced by bisindolylmaleimide I in SHR arteries. In WKY arteries, the pressure-dependent increase in myogenic tone was decreased to a similar extent by Y-27632 and bisindolylmaleimide I. These results suggest greater myogenic tone with increased calcium sensitization in SHR arteries, largely because of Rho kinase activation, with a minor contribution of PKC activation