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Effects of plasma factor(s) on vascular smooth muscle function and its role in the etiology of essential hypertension

University of British Columbia

Some recent investigations suggest that there exists a circulating factor in the plasma from patients with high blood pressure that sensitizes the vascular smooth muscle (Cappuccio et al. 1986). The present investigation was to determine if any circulating plasma factor could be detected in the hypertensive patients which alters the vascular smooth muscle functions of isolated blood vessels from the rat. Human plasma was obtained from normotensive and hypertensive subjects who were not on medication. Vascular strips were prepared from aortae and portal veins of normotensive wistar rats (Wt. 250 ± 50g) and placed in physiological solution in muscle baths. Contractile activities of aortic or portal vein strips in response to agonists (noradrenaline (NA) or potassium (K⁺) in the absence or presence of plasma from hypertensive patients, normotensive people and spontaneous contractile activity of portal vein in the presence of normotensive plasma, hypertensive plasma or human plasma proteins (albumin, gamma globulin, alpha (β) and beta (α) globulin, alpha (β) globulin and immunoglobulin IgG obtained commercially) were determined. As well as, possible mechanisms involved in the alteration of contractile response of the vascular smooth muscles in response to the various plasma proteins were examined using Ca⁺⁺ antagonists and receptor antagonists and ouabain in order to determine if the changes were dependent on specific membrane receptors, influx of Ca⁺⁺ through Ca⁺⁺ channels or the membrane receptors of the vascular smooth muscle cells. The results show that the aortic strips exposed to hypertensive plasma developed greater force to NA but less force to K⁺ compared to the aortic strips exposed to normotensive plasma. When the portal veins were exposed to hypertensive plasma its spontaneous activity was completely lost at the end of 20 min, but the portal veins exposed to normotensive plasma retained a very small percentage of this spontaneous activity. NA did not produce any response in the portal veins exposed to hypertensive or normotensive plasma but response to K⁺ in the presence of normotensive plasma was greater than that of hypertensive plasma. Increasing concentration of normotensive or hypertensive plasma increased the spontaneous activity of the portal vein up to 50 concentration of the plasma. Further addition of either of the splasma inhibited the spontaneous activity. The responses obtained in the presence of hypertensive plasma was significantly greater than the corresponding concentration of normotensive plasma. The plasma fractions albumin and gamma globulin both increased the spontaneous activity of the portal vein. In contrast the β-globulin alone or β- and α-globulin together inhibited the spontaneous activity. Immunoglobulin IgG which is about 70 of the gamma globulin fraction also increased the spontaneous activity of the portal vein. Phentolamine an β-adrenoceptor antagonist, blocked the increased spontaneous activity produced by albumin in the portal vein. Depolarizing the portal vein with ouabain did not have any influence on the spontaneous activity produced by albumin. Albumin still increased the spontaneous activity of portal veins denervated by 6-hydroxy dopamine. Depolarizing the portal vein with ouabain completely blocked the increase in the spontaneous activity produced by gamma globulin. Blocking the β-adrenoreceptors, cholinergic receptors, histamine receptors, serotonin receptors or angiotensin receptors did not block the increased spontaneous activity produced by gamma globulin. Blocking the calcium channel by verapamil also blocked the increased spontaneous activity produced by gamma globulin. The studies with aortic strips exposed to normotensive and hypertensive plasma to NA or K⁺ support the idea that there exists a vascular sensitizing agent in the hypertensive plasma. The studies of spontaneous activity of portal vein in the presence of plasma also indicate that there is a vascular sensitizing agent in the hypertensive plasma. The studies with plasma fractions on the spontaneous activity of the portal veins suggest that the vascular sensitizing agent may originate in the IgG fraction of the gamma globulin. The increased vascular tone produced by gamma globulin seems dependent on the membrane potential of the vascular tissue and the influx of Ca⁺⁺ through the Ca⁺⁺ channels.

Text

2010-08-22

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http://hdl.handle.net/2429/27616

Pharmacology and Therapeutics

University of British Columbia

UBCV

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