A Study of Smooth Muscle Relaxation in Rat Vasculature

Morrison, Keith John (1988) A Study of Smooth Muscle Relaxation in Rat Vasculature. PhD thesis, University of Glasgow.

Abstract

This study examined vascular smooth muscle relaxation in rat isolated aortic rings and related mechanical responses of tissues to the causative intracellular events. The main areas of research investigated were: (i) vascular relaxation induced by the bovine inhibitory factor; (ii) the effects of the contractile agents used to raise muscle tone on the degree and nature of vascular relaxation; and (iii) vascular relaxation in aortic rings from spontaneously hypertensive rats (SHR). The principal results obtained in this study are summarised be low: 1) The bovine inhibitory factor induced weak endothelium- independent relaxations of rat aortic rings precontracted with noradrenaline (1.6 x 10e-8M). 2) The inhibitory factor (100 mul) completely inhibited muscle tone raised with noradrenaline (1.6 x 10-8M) in rabbit aortic strips. The relaxant efficacy of the inhibitory factor may therefore be species-dependent. 3) Acetylcholine (10 -5M) and sodium nitroprusside (10 -6M) induced approximately the same degree of relaxation of aortic rings precontracted with noradrenaline (1.6 x 10M). 4) Sodium nitroprusside (10-6M) induced levels of cyclic GMP that were 10-fold higher than those induced by acetylcholine (10-5M). 5) The inhibitory factor (200 ul) did not significantly increase levels of cyclic GMP associated with weak vascular relaxation. 6) Acetylcholine and sodium nitroprusside, at concentrations that induced the same degree of relaxation as the inhibitory factor (200mul), did not significantly increase levels of cyclic GMP. 7) Sodium nitroprusside induced almost complete inhibition of muscle tone raised with noradrenaline (1.6 x 10 M) without increasing levels of cyclic GMP. These results suggest that the absolute levels of cyclic GMP measured during vascular relaxation may be of less importance than some other intracellular parameter. 8) Acetylcholine and sodium nitroprusside induced weaker relaxations of aortic rings precontracted with KCl (20mM) than of tissues precontracted with noradrenaline (1.6 x 10-8M). 9) Acetylcholine (10 -5M) and sodium nitroprusside (10-6M) induced smaller increases in the levels of cyclic GMP in tissues precontracted with KCl (20mM) than in tissues precontracted with noradrenaline (1.6 x 10 -8M). 10) Acetylcholine and sodium nitroprusside induced weaker relaxations of aortic rings precontracted with phorbol 12-myristate 13-acetate (PMA) (5 x 10 -7M) than of aortic rings precontracted with noradrenaline (2 x 10 -7M). 11) The levels of cyclic GMP induced by acetylcholine (10 -5M) and sodium nitroprusside (10 -6M) in tissues precontracted with PMA (5 x 10 -7M) were significantly smaller than in tissues precontracted with noradrenaline (2x10 -7M). These results contradict findings 3)-7) and show that the absolute levels of cyclic GMP measured during vascular relaxation are related to the degree of smooth muscle relaxation. 12) Noradrenaline induced concentration-dependent increases in the rate of hydrolysis of Ptd Ins, monitored by measuring the levels of Ptd OH. 13) KCl (30mM) and PMA (5 x 10 -7M) did not significantly increase the rate of Ptd Ins hydrolysis. 14) Acetylcholine (10 -5M) and sodium nitroprusside (10 -6M) respectively, significantly decreased the rate of Ptd Ins hydrolysis induced by noradrenaline (2 x 10 -7M). 15) Acetylcholine (10 -5M) and sodium nitroprusside (10 -6M) did not significantly alter the rate of Ptd Ins hydrolysis measured in response to KCl (30mM) or PMA (5 x 10 -7M). These results suggest that hydrolysis of Ptd Ins may first be necessary before potent vasorelaxations of aortic rings associated with increased levels of cyclic GMP can be demonstrated. 16) Throughout this study, sodium nitroprusside induced significantly greater relaxations than acetylcholine of precontracted aortic rings. This phenomenon was particularly marked in aortic rings precontracted with PMA (5 x 10 -7M). 17) Nitric oxide, which is the terminal mediator of vascular relaxations induced by both acetylcholine and sodium nitroprusside, induced powerful, concentration-dependent, endothelium-independent and transient relaxations of aortic rings precontracted with noradrenaline (2 x 10 -7M).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Pharmacology
• Date of Award: 1988
• Depositing User: Enlighten Team
• Unique ID: glathesis:1988-77711
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jan 2020 11:53
• Last Modified: 14 Jan 2020 11:53
• URI: https://theses.gla.ac.uk/id/eprint/77711