Olusoga A. Sofola

ALTERED RESPONSES OF AORTIC SMOOTH MUSCLE FROM SPRAGUE-DAWLEY RATS WITH SALT-INDUCED HYPERTENSION

1. The contractile responses of aortic ring preparations from Sprague‐Dawley rats made hypertensive by 6‐week dietary salt loading were studied. The test and control diet contained 8.0 and 0.3% NaCl, respectively. Aortic rings from salt‐loaded rats showed enhanced sensitivity to nor‐adrenaline (NA) but not to serotonin. Contractile responses to CaCl2 in Ca‐free NA‐containing medium was significantly enhanced in salt‐loaded rats, but was unchanged in K+‐depolarised medium. K+induced relaxation (a functional indicator of Na‐K adenosine triphosphatase activity) was sensitive to 10 μmol/L ouabain and was significantly attenuated in aortic rings from salt‐loaded rats. The results suggest that hypertension induced by salt‐loading is associated with enhanced sensitivity to NA, increased Ca2+ entry through receptor‐operated channels, and impairment of Na‐K ATPase enzyme activity.

EFFECT OF DIETARY SALT LOADING AND HIGH‐CALCIUM DIET ON VASCULAR SMOOTH MUSCLE RESPONSES AND ENDOTHELIUM FUNCTION IN RATS

1. The present study examined the effects of concurrent manipulation of dietary calcium and salt on contractile responses of vascular smooth muscle (VSM) and endothelial function of aortic rings from Sprague‐Dawley rats.

Mechanism of relaxant effect mediated by an aqueous extract of Hibiscus sabdariffa petals in isolated rat aorta

AbstractThe mechanism by which aqueous extracts of Hibiscus sabdariffa (HS) relaxes the vascular smooth muscle has been investigated. We used 2 mm ring segments of isolated aorta of rat mounted in organ baths containing physiological salt solution (PSS). Cumulative addition of HS (0.02—0.96 mg/ml) had a significant (p < 0.05) relaxation effect on noradrenaline precontracted rings but not on potassium chloride (KCl) precontracted rings. Similarly, HS significantly attenuated the contractile response to calcium chloride (CaCl2) in noradrenaline stimulated rings while it has no effect on KCl-stimulated rings. HS also significantly reduced the magnitude of noradrenaline phasic contraction. The results of this study suggest that HS relaxes vascular smooth muscle via a mechanism that is associated with an inhibition of Ca2+ influx through receptor operated channels and also on inhibition of Ca2+ release from intracellular stores.

The effects of calcium ions on the depression of cardiac contractility by chloroquinine and quinine

The effects of chloroquine or quinine, 0.04 mg. ml-1 on the ventricular function curve of turtles were determined. Both drugs caused a shift of the curve to the right indicating a reduction in cardiac contractility. This depression of the curve was fully reversed on raising the external calcium concentration from 1.1 mmol.1-1 to 5.8 mmol.1-1 in the case of chloroquine and to 6.7 mmol.1-1 when quinine was used. The observations indicate that calcium ions are able to reverse the cardiodepression induced by chloroquine and quinine.

Contractile response of normotensive rat aorta to serum from salt-loaded Sprague-Dawley rats.

Sprague-Dawley rats were made hypertensive by 6-week dietary salt loading with 8% NaCl in the diet and compared with control rats which had normal feed and water. At the end of this period, the salt-loaded group developed hypertension but the heart rate did not differ significantly from control.Serum taken from salt-loaded rats showed enhanced vasoconstrictor effect on normal rats aorta when compared with controls. This enhanced vasoconstrictor effect was attenuated by adrenergic receptor blockers but not by serotoninergic blockers. Thus salt loading may induce accumulation of vasoactive agents in the blood of rats.

Relaxation response of abdominal aorta to androgens in orchidectomised Sprague–Dawley rats fed a high-salt diet

Previous studies have demonstrated the acute relaxant effects of androgens on normal arterial beds, but not on any with underlying or induced pathologies. This study investigated whether the status of the gonads affects the direct actions of androgens on isolated abdominal aorta from male Sprague-Dawley rats fed a high-salt diet. A high-salt diet reduced the relaxation response to exogenous testosterone, but not to dehydroepiandrosterone (DHEA). Orchidectomy reduced the relaxation response to both testosterone and DHEA, while testosterone replacement restored the acute vasorelaxant effect of testosterone and DHEA in both normal and high-salt diet fed rats. Gonadal status appears to be important in the acute vasorelaxant effect of androgens.

Testosterone relaxes abdominal aorta in male Sprague–Dawley rats by opening potassium (K+) channel and blockade of calcium (Ca2+) channel

AIM To investigate the direct effect of testosterone and its precursor/derivative dehydroepiandrosterone (DHEA) on isolated rat abdominal aortic rings. MATERIALS AND METHODS 3mm abdominal aortic rings that were obtained from 3 months old male Sprague-Dawley rats were suspended in organ baths containing Hepes buffered PSS bubbled with 100% oxygen. Relaxation response to testosterone and DHEA was studied in noradrenalin pre-contracted rings. The role of aromatase and androgen receptor was assessed by inhibition using aminogluthetemide and blockade using flutamide respectively. Relaxation responses of the rings to testosterone in the presence of l-NAME, indomethacin, barium chloride, apamin, charybdotoxin, iberiotoxin, and nifedipine were also determined. RESULTS Both aromatase inhibition and androgen receptor blockade did not block the relaxing effect of testosterone on rings from rat abdominal aorta. Also there was no significant difference between testosterone relaxation response in the presence or absence of l-NAME and indomethacin. However 3μM, BaCl(2) almost completely abolished the aortic ring relaxation response to testosterone while 1μM, nifedipine potentiated the vasorelaxing effect of testosterone. CONCLUSION Testosterone relaxes abdominal aorta directly via a non-genomic pathway which is independent of endothelial derived vasoactive substances, but involves activation of inward rectifying potassium channel (K(IR)) and blockade of l-type calcium channel.

Relaxation responses of aortic rings from salt-loaded high calcium fed rats to potassium chloride, calcium chloride and magnesium sulphate

Abstract The relaxation responses of aortic rings of rats fed either normal rat feed, 8% salt diet, 8% salt+2.5% Ca diet or 2.5% Ca diet for 6–8 weeks has been investigated. The mean arterial pressure of salt loaded rats (148.63±8.54 mmHg) was higher ( P P 2 ( P P −1 significantly ( P 4 in aortic rings from all the groups. The result of this study indicates that salt-loading caused significant increase in the blood pressure of the rats and also reduced the relaxation responses of the aortic rings to KCl, MgSO 4 and CaCl 2 which suggest altered Na + ,K + -ATPase activity and resistance of the vascular smooth muscle membrane to calcium-induced membrane stabilization. These defects were reversed by dietary calcium supplement.

Haemodynamic changes during experimental tetanus toxicity in dogs

SummaryHaemodynamic variables were compared in control dogs, dogs with local tetanus toxicity and dogs with generalised tetanus toxicity. The results showed an increase in the inotropic and chronotropic activation of the heart in both groups of tetanus dogs, but there was no significant change in the mean systemic blood pressure and the common carotid occlusion reflex was unchanged.Spontaneous fluctuations in the systemic blood pressure were observed in some dogs with tetanus, and occurred more often in those with generalised tetanus. The modification of these fluctuations by beta-adrenergic blockade and diazepam, suggest that they are of autonomic neural origin.It is suggested that these changes in the cardiovascular system are the results of neurophysiological and biochemical changes in the sympathetic nervous system, which have been reported to occur in tetanus.

Role of the endothelium in the vascular effects of vitamin C in rats

The present study was undertaken to determine whether vascular responsiveness and endothelial function were altered in rats after 8 weeks of vitamin C treatment. Thoracic aortae were isolated from control and vitamin C-treated rats and analysed for changes in vascular reactivity. Vitamin C treatment attenuated the contractile response of aortic rings to noradrenaline and KCl. Removal of the endothelium increased the sensitivity of control rings but did not alter the effect of vitamin C. Endothelium-dependent relaxation to acetylcholine was significantly (P<0.05) enhanced by vitamin C, but the endothelium-independent relaxation response to sodium nitroprusside was not affected by vitamin C. The results suggest that the endothelium is not involved in the reduction in vascular sensitivity to contractile agonists caused by vitamin C. In addition, the enhancement of endothelium-dependent relaxation may be due to protection of nitric oxide against inactivation by oxygen free radicals.