ABSTRACT
The effect of Acetylsalicylic acid (ASA) on the responsiveness of rat aortic smooth muscle was investigated by comparing the contractility of aortic rings from SHR and WKY rats in response to alpha-agonist, phenylephrine (PE). Cumulative dose response curves for PE were generated from aortic rings of SHR and WKY rats in the presence and absence of 0.2mM ASA. To investigate the involvement of endothelium on ASA mediated effects, active tension was recorded for denuded and non-denuded rings from SHR animals in response to KCl and PE. Denuded and non-denuded aortic rings from SHR animals in the presence of ASA produced significantly higher active tension than in the absence of ASA. The reactivity of aortic rings from WKY control animals was not altered significantly in the presence of ASA. These studies suggest that ASA can also modulate aortic contractility through other mechanism(s) in addition to its effect on the metabolites of arachidonic acid. Significance of these observations is discussed below.
Subject(s)
Aspirin/pharmacology , Hypertension/prevention & control , Muscle, Smooth, Vascular/drug effects , Phenylephrine/pharmacology , Vasoconstriction/drug effects , Animals , Aorta, Thoracic/drug effects , Male , Rats , Rats, Inbred SHR , Rats, Inbred WKYABSTRACT
The effects of acetylsalicylic acid (ASA), on aortic smooth muscle contractility during hypertension were studied in female SHR and WKY rats. The rats were administered two intraperitoneal injections of 10 mg/kg of ASA per week for three weeks. Twenty four hours after the last injection the aortic smooth muscles were evaluated for generation of active tension in response to KCl, phenylephrine, clonidine and norepinephrine. We report that aortic rings from ASA-treated SHR animals were more responsive than rings from non-treated SHR female rats. ASA treatment of SHR animals restored the contractile response to the level shown by non-treated WKY control female rats. The response from aortic rings of ASA-treated SHR to KCl, phenylephrine and clonidine was essentially similar to the response of rings from non-ASA-treated WKY control female rats. We did not observe any decrease in the systolic blood pressure during the ASA treatment in SHR female rats. These results suggest that acetylsalicylic acid modulates aortic smooth muscle contractility either through the metabolites of arachidonic acid or through alpha-adrenoceptors.
Subject(s)
Aspirin/pharmacology , Hypertension/physiopathology , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Adrenergic alpha-Agonists/pharmacology , Animals , Aorta/drug effects , Blood Pressure/drug effects , Clonidine/antagonists & inhibitors , Female , Hypertension/drug therapy , In Vitro Techniques , Membrane Potentials/drug effects , Norepinephrine/antagonists & inhibitors , Phenylephrine/antagonists & inhibitors , Potassium Chloride/pharmacology , Rats , Rats, Inbred SHR , Rats, Inbred WKYABSTRACT
The effects of caffeine on aortic smooth muscle contractility during hypertension were studied in SHR and WKY control rats. To compare the effects of Mg++ on vascular reactivity induced by caffeine 1.2 mM MgCl2 was either included or omitted from the Krebs solution bathing the aortic tissue. The role of alpha-adrenergic receptors and verapamil-sensitive Ca++ channels in eliciting caffeine induced contraction in aortic tissues was also examined in Sprague Dawley rats. We report that the aortic smooth muscle from SHR animal was less responsive than WKY aortic smooth muscle to 10 and 20 mM concentrations of caffeine. Caffeine induced a relaxation of aortic smooth muscle contracted with 60 mM KCl or 10(-7) M NE. However, the relaxation response was slower in SHR as compared to WKY rats. To assess the involvement of alpha-adrenergic receptors in caffeine induced aortic contractility alpha 1- and alpha 2-receptors were blocked with 10(-7) M prazosin and 10(-7) M yohimbine respectively. The caffeine induced aortic contractility did not seem to involve alpha-adrenergic receptors. A blockade of verapamil sensitive Ca++ channels with 10(-7) M verapamil failed to inhibit caffeine induced aortic contractility. These results indicate that caffeine involves release of Ca++ in vascular muscle, however, Ca++ is released from a site other than the one controlled by alpha-adrenergic receptors. Also, the Ca++ channels involved are other than the Verapamil sensitive Ca++ channels. Yet it is clear that if the aortic contractility is due to Ca++ release alone, then caffeine is a potent agent for Ca++ release in the aortic smooth muscle of rat. Additionally, the caffeine-sensitive mechanism for aortic smooth muscle contraction is impaired during hypertension.
