The small arteries play an important functional role in establishing the increased peripheral resistance found in essential hypertension. This paper concerns the direct measurement of the intrinsic mechanical and contractile properites of two categories of small arterial resistance vessels in the mesenteric bed of 5-month-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The vessels had mean internal diameters of 246 fim and 153 /*m when relaxed at 100 mm Hg effective transmural pressure. Segments (1 mm) were mounted in such a way that internal circumference could be controlled and the circumferential wall tension (T) measured. After mounting, each vessel was maximally activated (by K* depolarization at 37°C in the presence of 5 mM Ca) at an internal circumference for which AT was approximately maximal, where AT = Tactlve Trelaxed. From the average values of AT measured we have estimated (on the basis of Laplace's equation) that the SHR vessel would average values of AT measured we have estimated (on the basis of Laplace's equation) that the SHR vessels would have been able to contract against 34% greater pressures than the WKY vessels (P < 0.001). Optical measurements of the dimensions of these vessels showed a 23% greater wall thickness in the SHR vessels (P < 0.02). There were no significant differences in the calculated active wall stresses of the SHR and WKY vessels; this suggests that the greater contractility found in the SHR vessels may be due to their having a greater smooth muscle cell content. These vessel measurements have been examined as well as the rats' blood pressures and heart to body weight ratios. The comparison points to the possibility that the disturbance to the cardiovascular regulatory system which results in hypertension produces similar cellular responses in both the myocardium and the peripheral vasculature.

Contractile Properties of Small Arterial Resistance Vessels in Spontaneously Hypertensive and Normotensive Rats

The detrusor smooth muscle is the main muscle component of the urinary bladder wall. Its ability to contract over a large length interval and to relax determines the bladder function during filling and micturition. These processes are regulated by several external nervous and hormonal control systems, and the detrusor contains multiple receptors and signaling pathways. Functional changes of the detrusor can be found in several clinically important conditions, e.g., lower urinary tract symptoms (LUTS) and bladder outlet obstruction. The aim of this review is to summarize and synthesize basic information and recent advances in the understanding of the properties of the detrusor smooth muscle, its contractile system, cellular signaling, membrane properties, and cellular receptors. Alterations in these systems in pathological conditions of the bladder wall are described, and some areas for future research are suggested.

https://www.physiology.org/doi/pdf/10.1152/physrev.00038.2003

Urinary bladder contraction and relaxation: Physiology and pathophysiology

The mechanical and morphological properties of segments of certain precisely defined resistance vessels (approximately 150 micrometer lumen diameter) in the mesenteric bed of spontaneously hypertensive (SHR) and normotensive (WKY) rats have been compared in vitro under carefully controlled conditions and also after fixation. At a given transmural pressure, the relaxed SHR vessels (compared with the WKY vessels) would have had a 16% smaller lumen diameter (P less than 0.01) and a 49% thicker media (P less than 0.005), so that the media volume per unit segment length was 31% greater (P less than 0.05). The smooth muscle cells were arranged circumferentially in about four layers in the SHR vessels and in about three layers in the WKY vessels. The SHR active wall tension in response to potassium was 53% greater (P less than 0.02) and to norepinephrine was 50% greater (P less than 0.01) than for WKY. However, the ED50 values for the norepinephrine dose-response curves were similar (approximately 5 micrometer). Activation with potassium plus norepinephrine gave greater responses in both vessel types, than with either agent alone, but the SHR responses were on average only 19% greater than the WKY (P less than 0.10). However, under these conditions, the SHR vessels would have been able to contract against 45% greater transmural pressures (P less than 0.001) because of their smaller lumen. On maximal activation, the mean force developed by each cell (approximately 3.85 micro N) was the same in both vessel types, even though on average (P = 0.10) the SHR cells had a 21% greater cross-sectional area. The results support the Folkow hypothesis that in genetic hypertension the increased peripheral resistance is associated with structural changes in the resistance vessels.

Direct evidence that the greater contractility of resistance vessels in spontaneously hypertensive rats is associated with a narrowed lumen, a thickened media, and an increased number of smooth muscle cell layers.

A sensitive device for recording of mechanical activity in isolated small blood vessels with calibres down to 100 microns is described. This equipment was used to examine the mechanical properties of rat cerebral arteries. The ultrastructure of the preparations was investigated by light-, transmission, and scanning electron-microscopy. In general the walls of the middle cerebral and basilar arteries consisted of 3 layers of smooth muscle cells, which occupied approximately 80% of the total wall thickness. The present technique preserved the integrity of the vessel wall and caused no observable damage to the smooth muscle or endothelial cells. Neither the basilar nor the middle cerebral arteries developed spontaneous phasic contractions under standard conditions. Potassium excess (124 mM) induced a biphasic contractile response characterized by a fast and partly transient increase in tension (phase A), followed by a slowly developing sustained contraction (phase B). The responses to K+ were strong, highly reproducible and not influenced by pH changes in the range 6.9-7.8, making K+-stimulation suitable for testing of vascular contractility. Length-tension measurements were performed on relaxed and K+-activated basilar arteries. The mechanical behaviour of the vessels conformed to a sliding-filament model of muscular contraction. Using the "Maxwell model" of a muscle, the length at which the contractile element produced maximum active tension was established. The passive wall tension at this length (approximately 1 mN/mm) averaged only about 20% of the total wall tension the arteries were capable of producing when activated by K+. Under isometric conditions the K+-contracted basilar artery developed a maximum active wall stress of approximately 240 mN/mm2. In the light of the mechanical data obtained from the length-tension measurements, the optimum resting wall tension for registration of vascular responses is discussed. It appears that the present in vitro system can be of great value in investigations of the smooth muscle function in small blood vessels.

Mechanical properties of rat cerebral arteries as studied by a sensitive device for recording of mechanical activity in isolated small blood vessels.

ALTHOUGH the histology and ultrastructure of smooth muscle cells have been studied extensively there is little direct evidence concerning their mechanical properties. Their small size1,2 and lack of tendon connections have prevented them from being mounted on a myograph, as has been done with striated muscle fibres3. Moreover, their multiplicity and optical properties make it difficult to visualise them in whole smooth muscle preparations. Although isolated smooth muscle cells4–6 can be seen to contract when stimulated, it has not been possible to measure the forces they develop. There are, therefore, still serious doubts about the extent to which the mechanical properties of whole smooth muscle preparations are an accurate reflection of the properties of smooth muscle cells. We have therefore developed a technique to obtain mechanical data from a smooth muscle preparation which only contains about 1,000 smooth muscle cells, and which is thin enough for the cells to be visualised by Nomarski interference microscopy7. This technique provides for the first time the means to study the mechanical properties of smooth muscle cells in situ.

Mechanical properties of vascular smooth muscle cells in situ.

After correction for extracellular space (40%) determined from electron micrographs, the maximum isometric force developed by strips prepared from the media of the hog carotid artery (2.2 x 106 dyn/cm2) can be extrapolated to give a value of 3.7 x 106 dyn/cm2 for the smooth muscle component of the strip. Three independent estimates of the myosin content of the smooth muscle cells were made based on (a) exhaustive extraction and purification with estimates of preparative losses, (b) the myosin catalyzed ATPase activity of media homogenates, and (c) quantitative densitometry of the peaks containing myosin, actin, and tropomyosin after disk electrophoresis of sodium dodecyl sulfate-treated media homogenates. The results were consistent and gave a myosin content of 5–10 mg/g media, or 8–17 mg/g cell. Method (c) gave myosin:actin:tropomyosin weight ratios of 1:3.2:0.8. Although measured force developed by the smooth muscle cell exceeds that of mammalian striated muscle, the myosin content in smooth muscle is about five times lower. The actin content of smooth muscle is relatively high. The actin and myosin contents are consistent with thick and thin filament ratios observed in electron micrographs of vascular smooth muscle.

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J. Megerman

Papers

Force-generating capacity and contractile protein content of arterial smooth muscle.