Attenuation of blood flow-induced dilation in arterioles after muscle contraction.

The response of third-order arterioles (n = 15) in rat cremaster muscle to increased luminal flow was studied after brief (20-30 s) occlusion of a neighboring arteriole in pentobarbital-anesthetized rats. Red cell velocity increased almost fivefold (485 +/- 54% of control) during occlusion, and vessel diameter increased 63 +/- 11%. Initially, the calculated wall shear rate increased to 430 +/- 40% of control during occlusion but then decreased to 308 +/- 35% of control as a consequence of arteriolar dilation. The muscle was subsequently stimulated to contract for 1 min, and the occlusion procedure was repeated after arteriolar diameter and red cell velocity had returned to control levels. In this instance the vessel dilation was 34 +/- 10% or about one-half of that seen during the previous occlusion, although velocity and shear rate rose to a similar degree (474 +/- 54 and 397 +/- 35%, respectively). Dilation during a third occlusion 2-7 min after the vessel recovered from the second occlusion was as great as during the first occlusion (77 +/- 20%). The results indicate that flow-induced dilation in arterioles of rat cremaster muscle is transiently attenuated after muscle contraction.

Contractility of the rabbit abdominal aorta 4 days after endothelium denudation.

The purpose of this study was to evaluate contractility of the rabbit abdominal aorta 4 days after de-endothelialization by balloon catheter. The isometric tension of ring-segments in response to vasoactive agents was monitored. A significant enhancement of contraction to noradrenaline and serotonin was found in aortas 4 days after endothelium denudation as compared with controls with endothelium. The enhancement, however, did not differ from that found already in acutely denuded vessels (immediate denudation). No significant difference in contractility to potassium chloride was found in either group of denuded preparations as compared with controls. The sensitivity to all three vasoactive agents (EC50) was not influenced by denudation. These results indicate that changes in the contractility of denuded vessels are predominantly a consequence of lacking the endothelium as a producer of endothelium-derived relaxing factor. The access of mitogens to the media does not seem to interfere with the magnitude of contraction 4 days after denudation.

Interaction of prostaglandins and the myogenic factor in the mechanism of closure of the ductus arteriosus.

Although the role of prostaglandins (PG) in the mechanism of dilatation of the ductus arteriosus (DA) has received considerable attention, no data on their possible interaction with the pressure-induced myogenic reaction are available. There is also a lack of information on PG production by the foetal blood vessels of the guinea-pig, in which the DA closes rapidly. Use of the RIA method showed relatively low PG production by isolated foetal guinea pig blood vessels, as represented by the main products, PGI1 and PGE2. When computed in pmol per mg wet weight, the production of 6-keto-PGF1 alpha (an equivalent of PGI2) was statistically significantly higher in the foetal DA (4.06 +/- 1.13) than in the foetal aorta (2.04 +/- 0.33). The isolated DA reacts to a sudden increase in perfusion pressure by marked constriction, which in some cases leads to functional closure of the DA. In 10(-7) to 10(-5) mol.l-1 concentration, PGE2 reversibly inhibits pressure-induced myogenic constriction, while under the same conditions the contractility of the DA in response to oxygen is unaffected. In concentrations of 10(-6)-10(-5) mol.l-1, indomethacin, a blocker of PG biosynthesis, also induces pressure constriction and it raises the basal flow resistance of isolated DA preparations. The results indicate that PGs play a modulator role in the pressure myogenic response of the DA of guinea-pig and rabbit foetuses.

Dilator response of rat mesenteric arcading arterioles to increased blood flow velocity.

Arcading arterioles (average diam 68 microns ID) connecting adjacent triangular vascular sectors in the rat mesentery were examined in vivo for the presence of flow-dependent vasodilation. When a feed artery to one of these sectors was occluded, the affected sector was supplied by collateral flow through the arcading arteriole, and red cell velocity in the arteriole increased by 10-66 mm/s. The velocity increase was followed (with an average delay of 7.7 s) by dilation of the arcading arteriole, which averaged 68%. The dilation was closely correlated with red cell velocity (r = 0.96), volume flow (r = 0.96), and wall shear rate (r = 0.89). The dilation was sustained for the duration of increased velocity (1-10 min) and was not affected when direction of flow in the arteriole was reversed. The flow-induced dilation was equal to the maximal dilation attained with topically applied papaverine. Dilation of the arcading arteriole could be almost completely abolished if the arteriole was also occluded during occlusion of a feed artery. These observations indicate that a potent flow-dependent dilator mechanism is present in arcading arterioles of rat mesentery and may play an important role in local regulation.

Flow-induced dilation of the dog gracilis muscle artery.

The external diameter of the artery (1.08 +/- 0.04 mm) predominantly supplying the gracilis muscle was monitored in situ in 12 dogs under thiopental anaesthesia using a contact inductive transformer. The blood flow in the artery could be controlled by an arteriovenous shunt. After a latency of 10.6 +/- 0.7 s, an increase of blood flow through the artery from 4.0 +/- 0.3 to 45.0 +/- 3.4 ml.min-1 induced an increase in its diameter by 44.9 +/- 3.6% of the resting value (p less than 0.001). When the blood flow-rate was reduced to the initial level, the artery constricted with a half-recovery time of 307.2 +/- 30.7 s. The amplitude and the time course of the arterial dilation were identical when the blood pressure at the site of diameter measurement decreased or remained unchanged. The dilation became maximal at blood flows corresponding to the peak of reactive hyperaemia in the gracilis muscle after 2 min arterial occlusion. It is being suggested that the blood flow-induced dilation ensures autostabilization of conduit artery function.

Dilatation of conduit coronary artery induced by high blood flow.

The ramus interventricularis ventralis (RIV) of the dog heart was perfused with donor blood from the femoral artery. The inflow and outflow pressure, the blood flow and the diameter of the RIV were recorded. An increase in the blood flow from 11.3 +/- 0.3 to 81.4 +/- 6.2 ml/min induced, in 24.4 +/- 1.7 s a gradual increase in RIV diameter which became stabilized in 90-120 s and amounted to 80.87 +/- 11.68 microns, i.e. to 3.37 +/- 0.70% of the resting diameter. Since the mean pressure at the site where the diameter was recorded was maintained constant, relaxation of RIV smooth muscle has been assumed to have occurred. Dilation could not be evoked after RIV had been dilated by papaverine. Any interference by changes in pressure amplitude accompanying the increase in blood flow was precluded by using non-pulsating perfusion of the RIV. An increase in the non-pulsating blood flow from 12.11 +/- 2.20 to 90.33 +/- 11.30 ml/min likewise--in 19.50 +/- 1.83 s--produced an increase in RIV diameter of 1.8%. Blood flow is being suggested as one factor regulating the tone of the smooth muscle of the major coronary artery. This mechanism is supposed to counteract sympathetic constriction of the major coronary artery.

Bayliss myogenic response in the isolated ductus arteriosus of guinea-pig and rabbit fetuses.

Isolated ductus arteriosus responds by marked constriction to increases in perfusion pressure. If, however, these increases exceed 90 mm Hg-130 mm Hg, the vessel suddenly dilates and its responsiveness becomes depressed. The importance of these findings in postnatal closure of ductus arteriosus is discussed.

Metabolic vasodilatation in skeletal muscle and the problem of the direct or indirect action of oxygen on resistant blood vessels.

1. Vasodilatation induced by venous blood infusion and reactive hyperaemia following the reduction of perfusion pressure for different lengths of time (1 to 128 sec) were studied in the haemodynamically isolated and denervated vascular bed of the dog gracilis muscle. The two local regulatory situations differed chiefly in respect to the oxygen concentration in the precapillary part of the blood bed (51.4% and 97.6% respectively) and in the size of the blood flow (100% and 48.5% of the resting value). 2. The interval between the time when venous blood entered the resistant precapillary vessels and the onset of the local regulatory response was 25.1 +/- 1.9 seconds. In prolongation of the duration of reduced perfusion pressure, the continuous increase in the maximum reactive hyperaemia value was interrupted, on reducing it for 16-32 seconds, by a significant (P less than 0.001) abrupt increase in this value. 3. We conclude from the good agreement of these two time values that: 1. reduction of the blood oxygen concentration to 51.4% does not directly affect the smooth muscle cells in the wall of resistant vessels; 2. an interval of 25.1 +/- 1.9 sec (16-32 seconds) is needed for interference with the metabolism of skeletal muscle to attain a critical value and for the relevant chemical signal to produce a dilatation response in the arterioles.

Work-induced potassium changes in skeletal muscle and effluent venous blood assessed by liquid ion-exchanger microelectrodes.

Using liquid ion-exchanger semimicroelectrodes with a side pore, we measured changes of extracellular potassium concentration (Ke+) in adult rabbit and cat gastrocnemius muscles and in venous effluent blood flowing from the cat gastrocnemius muscle during various bouts of activity induced by sciatic nerve stimulation. 1. Isometric tetanic contractions (at 50 Hz) of various durations caused transient accumulation of Ke+ which was non-linearly related to the duration of muscle activity. The peak values of Ke+ in response to muscle stimulation were analogous in rabbits and cats, attaining values, e.g. after a 20-sisometric tetanus, between 8-9 mEq/1K+ in both species. 2. Potassium concentration in venous effleunt blood (K+ven) was transiently increased after isometric tetani. Since blood flow was measured at the same time, it was possible to calculate the amount of K+ lost by the muscle after tetani of various durations. A 32 g gastrocnemius muscle of the cat, for example, loses 9.36 +/- 1.52 muEqK+ after a 20-s isometric tetanus, which corresponds roughly to 0.5% of the total muscle potassium content. The loss of K+ in this muscle was 29.3 pEq K+ /impulse/100 g fresh muscle tissue. 3. There was no evident difference between the amount of K+ released during isometric tetani, or tetanic contractions performed under isotonic conditions. Single twitches evoked by indirect stimulation at 1 HZ for several minutes also induced a small rise in K+ven. 4. If the loss of K+ from the muscle into the blood stream is transiently prevented by arterio-venous occlusion installed immediately before a 10-s isometric tetanus, most K+ is released subsequently when blood flow is renewed, if the occlusion lasts for 20-25 s. It is not until blood flow is occuded for 40-60 s that most K+ is apparently resorbed and only a minor portion is released and is to be found in the venous blood. 5. The transient accumulation of muscle extra-cellular potassium may locally affect nerve endings, skeletal and smooth muscle cells.