Anthony B. Ebeigbe

Dietary salt‐loading attenuates endothelium‐dependent relaxation in response to histamine but not to acetylcholine in rat aortic rings

Endothelium‐dependent relaxation in response to histamine and ACh has been studied on precontracted aortic rings from control and salt‐loaded Sprague‐Dawley rats. Both ACh and histamine caused relaxation of the noradrenaline‐induced precontraction only in the presence of the endothelium. The relaxation response to ACh in rings from control and salt‐loaded rats did not differ significantly whereas histamine‐induced relaxation was significantly attenuated in aortae from salt‐loaded rats. The results suggest that salt‐induced hypertension is associated with impairment of endothelium‐dependent relaxation to histamine but not to ACh.

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.

IN VITRO VASCULAR EFFECTS OF CICLETANINE IN PREGNANCY-INDUCED HYPERTENSION

1 The vascular effects of cicletanine have been studied in vitro on ring preparations of inferior epigastric arteries from normotensive human females and human females with pregnancy‐induced hypertension (preeclampsia). 2 Cicletanine (10−7–10−3 m) elicited concentration‐dependent relaxation of vessels precontracted with 10−7 m noradrenaline (NA) or 60 mm K+ but was more potent in the former. Relaxation was significantly greater in rings from preeclamptic patients and was uninfluenced by endothelium removal. 3 The intracellular Ca‐dependent contractile responses to 10−5 m NA in Ca‐free medium as well as the subsequent extracellular Ca‐dependent contractions (on restoration of external Ca) were significantly attenuated dose‐dependently by cicletanine (10−5 m, 3 × 10−4 m) in arterial rings from both normotensive and preeclamptic patients. Cicletanine also relaxed rings precontracted by 25 mm K+ but was ineffective against 80 mm K+‐induced contractions. 4 The inhibition of intracellular Ca‐dependent contractions was significantly greater in rings from preeclamptic than from normotensive patients whereas extracellular Ca‐dependent contractions were comparably inhibited in both groups. Nifedipine, on the other hand, had little effect on the intracellular Ca‐dependent contractions but significantly depressed extracellular Ca‐dependent contractions. 5 Cicletanine‐induced relaxation was uninfluenced by pretreatment with propranolol, ouabain, tetraethylammonium, procaine, indomethacin, cimetidine or tetrodotoxin but was antagonized by glibenclamide. 6 The results show that cicletanine inhibits contractile responses of human isolated inferior epigastric arteries by a mechanism unrelated to endothelial factors but associated with inhibition of calcium metabolism. An action of cicletanine on glibenclamide‐sensitive K+ channels is also suggested. Cicletanine‐induced inhibition was significantly greater in arteries from preclamptic patients.

Role of endothelium in magnesium-induced relaxation of rat aorta

SummaryThe role of endothelium in the relaxation of rat aortic smooth muscle to raised extracellular magnesium concentration (Mg2+)o has been examined.Following contractile responses to norepinephrine (NE) or high-K+ in Mg2+-free media, cumulative increases in (Mg2+)o caused concentration-dependent relaxations in intact (+ E) as well as endothelium-denuded (− E) strips. In NE-stimulated strips, Mg2+-induced relaxation was significantly greater in + E strips, whereas the reverse was the case in K+-stimulated strips.Bay K8644, a Ca2+ channel agonist, did not modify Mg2+-induced relaxation in NE-stimulated strips, but significantly attenuated the relaxation in K+-stimulated strips in the order: − E > + E.The results suggest that Mg2+-induced relaxation of rat aorta is associated, at least in part, with the release of an endothelium-derived relaxant factor in receptor-mediated, but not in depolarisation-dependent contractions.

Influence of NG-monomethyl-L-arginine on endothelium-dependent relaxations in the perfused mesenteric vascular bed of the rat

Endothelium-dependent relaxation mediated by the formation of nitric oxide (NO) from L-arginine, is prevented by the arginine analog NG-monomethyl L-arginine (L-NMMA) (Palmer et al., Biochem. Biophys. Res. Comm. 153:1251-1256 (1988)). In the rat mesenteric arterial bed, incubation with L-NMMA did not prevent acetylcholine-induced relaxation, which, however, was reversed when L-NMMA was added during its maximum effect. A similar profile of action was observed with methylene blue, an inhibitor of guanylate cyclase. Methylene blue, but not L-NMMA, increased basal perfusion pressure. These data indicate that in the mesenteric arterial bed, NO formation via the L-NMMA-sensitive pathway occurs during stimulation with acetylcholine, but not under basal conditions.

Vascular smooth muscle responses in pregnancy-induced hypertension

Abstract Despite numerous studies on cardiovascular changes associated with pregnancy-induced hypertension, the precise mechanisms underlying the increased peripheral vascular resistance remain poorly defined. A number of observations suggest that local mechanisms within the blood vessel wall could play a major role . Tony Ebeigbe and M. Ezimokhai highlight recent observations on changes within the vascular smooth muscle cell in preeclampsia as well as the effects of some vasoactive agents on critical control points within the vascular smooth muscle cell .

Effects of calcium channel blockade in canine saphenous veins after storage at −190°C

1 Canine saphenous veins were investigated in vitro either within 24 h after removal or after storage at −190°C for 4–5 weeks in foetal calf serum containing 1.8 m dimethyl sulphoxide. 2 Contractions and 45Ca2+ uptake in response to both depolarization and guanfacine were studied in the absence and presence of the calcium channel antagonists diltiazem, verapamil, nifedipine and the two stereoisomers of a 1,4‐dihydropyridine derivative, namely the (+)−(S) enantiomer and the (−)−(R) enantiomer of 202–791 (isopropyl 4‐(2,1,3‐benzoxadiazol‐4‐yl)‐l,4‐dihydro‐2, 6‐dimethyl‐5‐nitro‐3‐pyridinecarboxylate). 3 Comparison of the data obtained on unfrozen and frozen/thawed veins revealed a good preservation of both contractile responsiveness and 45Ca2+ uptake mechanisms after storage at −190°C. 4 It is suggested that cryopreservation is a useful technique for storing venous smooth muscle for pharmacological studies.

EFFECTS OF CICLETANINE ON HISTAMINE-INDUCED CONTRACTIONS OF ISOLATED RABBIT MESENTERIC ARTERIES

Summary— The antagonism by cicletanine of contractile responses to histamine has been examined in vitro on ring preparations of rabbit mesenteric arteries. Cicletanine (10‐8–10−6 M) caused a parallel rightward shift of histamine concentration response curve, with a pA2 value of 7.48 (slope = 0.89 ± 0.19, not significantly different from unity). Histamine‐induced contractions were nifedipine‐sensitive and associated with cicletanine‐sensitive increased 45Ca uptake.

Responses of Arterial Smooth Muscle from Normotensive and Pre-eclamptic Subjects to the Calcium Channel Agonist, Bay K 8644*

SummaryThe effect of Bay K 8644, a dihydropyridine Ca2+ agonist, on in vitro contractile responses of inferior epigastric arteries from normotensive (N) and pre-eclamptic (P) subjects has been investigated, with a view to further defining the mechanism of the increased vascular sensitivity associated with pregnancy-induced hypertension.Bay K 8644 (10−10−10−7M) caused dose-dependent contractions of N as well as P arteries under resting conditions in the order: P > N and caused development of rhythmic contractions in both N and P arteries. Bay K 8644 effects were prevented by 3 × 10−8M Nifedipine (a Ca+2 antagonist). Bay K 8644 also significantly (P < 0.05) enhanced the sensitivity as well as maximal contractile responses to CaCl2 in 40 mM K+-depolarized Ca-depleted N and P arteries in the order: P > N.The results suggest that the increased peripheral vascular sensitivity associated with pregnancy-induced hypertension may be due, at least in part, to enhanced activity of the potential-sensitive Ca2+ channels in arterial smooth muscle plasmalemma.

Endothelium-dependent rat aortic relaxation to the aqueous leaf extract of Musanga cecropioides

An aqeuous leaf extract of Musanga cecropioides (family: Cecropiaceae) is used in traditional medical practice to induce labour due to its oxytocic effect (Bouquet, 1969); it has also been reported to have a blood pressure lowering effect in humans (Bouquet, 1969). Agents that lower blood pressure could act via one of several vasodilator mechanisms (Bolton, 1979; Ebeigbe and Aloamaka, 1985). In the present paper, the possibility that M. cecropioides could have a direct vasodilating effect has been examined using isolated rat aorta.