Myogenic adaptation of rabbit ear arteries to pulsatile internal pressures.

1. The effect of sinusoidal internal pressures on the constriction of in vitro, pressurized segments of ear arteries from rabbits has been examined. All arteries were constricted against a static transmural pressure of 60 mmHg to 35-60% of maximal, using extraluminal noradrenaline, before being exposed to the sinusoidal pressures. 2. There was a short period of adaptation when active arteries were first exposed to physiological pulsatile pressures. This adaptation had two components: a small, largely transient distension, lasting about 1 min, and sustained suppression of the distension produced by individual pressure pulses. 3. Constriction of adapted arteries was insensitive to physiological changes in pulse frequency (3-5 Hz), mean pulsatile pressure (60-120 mmHg), pulse amplitude (20-40 mmHg) and to alterations in pulse shape (sinusoidal, triangular and ramp). Over-all distension was restricted to 3.6 +/- 1.0% (S.D. of an observation) when the mean of a 3 Hz sinusoidal pressure of 30 mmHg amplitude was increased in steps from 75 to either 115 or 120 mmHg. 4. An initial distension was needed to initiate suppression of pressure pulse distension. Distension by individual pressure pulses, within a train of rectangular 60-90 mmHg pulses of 0.5 s duration, was maximally suppressed (85.6 +/- 1.3%; S.E. of mean, n = 9) at a pulse interval of 0.7 s. 5. Active ear arteries possess a myogenic mechanism capable of minimizing changes in constriction over the full physiological range of pulsatile internal pressures.

The interaction between noradrenaline activation and distension activation of the rabbit ear artery.

Excised, pressurized segments of the rabbit ear artery have been used to examine the interaction between the transmural pressure and constriction of arteries by extraluminal noradrenaline. The bath temperature was kept at 32-33 degrees C to suppress instability and spontaneity of constriction. Fast, reproducible jumps in pressure were obtained by using a microcomputer to control an electropneumatic transducer. The arteries did not react actively to transmural pressure changes unless already activated by noradrenaline. Active arteries responded to distension by a pressure jump with a reproducible compensatory constriction which was unaffected by tetrodotoxin. The counteraction of distension was due primarily to enhanced activation of the muscle. Distension activation decreased with increasing constriction. Utilization of the force-generating capacity of the arteries either remained unchanged at 20-30% or, in one experiment, increased slightly when constriction against a transmural pressure of 60 mmHg was increased from 20 to 75% of maximal by raising the noradrenaline concentration. When the transmural pressure was 90 mmHg, the 35-55% utilization of the force-generating capacity either remained constant or fell as constriction was increased. Most of the force-generating capacity was available for counteracting the distension of moderately constricted arteries (less than 40% of maximal) produced by a 60-90 mmHg jump. More than 78% of the maximum capacity was used in attempting to overcome the distension when it was maintained by computer-controlled increases in transmural pressure. The moderate constrictions were produced with noradrenaline concentrations which were 500-10,000 times lower than that used to maximally activate the arteries. The rabbit ear artery possesses a powerful, distension-sensitive mechanism that acts to minimize diameter changes initiated by transmural pressure jumps. The diameter of the active artery was determined by a combination of noradrenaline activation and distension activation for constrictions up to at least 75% of maximal. It is concluded that the interaction between noradrenaline activation and distension activation helps the muscle to fulfil the special functional requirements imposed by the geometry of tubes. This type of myogenic control system may be particularly well developed in those muscular blood vessels exposed to pulsatile internal pressures.

Active reactions of the rabbit ear artery to distension.

Changes in the external diameter of active arteries, excised from the rabbit ear, were recorded following jumps in pressure within the arteries. The arteries were either spontaneously active or were constricted with noradrenaline. Active arteries dilated when the transmural pressure was jumped from 60 to 100 mmHg, but the dilatation was largely, sometimes completely, overcome by compensatory constriction within 1-2 min. Varying the constriction from 15 to 80% of the maximal constriction had no effect on the ability of the arteries to counteract distension. An average of 90 +/- 2% of the distension was overcome in 2 min and this was achieved against increases in stress (force/wall cross-sectional area) on the muscle of not less than 74%. Jumps in pressure rarely enhanced constriction and then only when constriction was slight (less than 15% of maximal). Restoring the transmural pressure to 60 from 100 mmHg produced a transient constriction when the initial constriction was less than 50% of the maximal constriction. The sequence of counteraction of distension and transient constriction on reversing the pressure jump was reproducible for many hours. Increasing constriction of the arteries first decreased and then, at maximal constriction, suppressed all transient changes in diameter. Smaller jumps in pressure produced less dilatation which was more readily prevented by increasing constriction. These results show that the wall of the ear artery possesses a pressure-sensitive, negative feed-back mechanism which minimized changes in diameter following jumps in pressure.

Constriction of ear arteries from normotensive and renal hypertensive rabbits against different transmural pressures.

Isolated segments of rabbit ear arteries were made to constrict against normotensive and hypertensive transmural pressures by perfusion with submaximal concentrations of norepinephrine (NE). Changes in load (force/unit length of artery) and stress (force/wall cross-sectional area) during constriction against a constant pressure have been evaluated. Weak concentrations of NE constricted the arteries equally well against transmural pressures of 80 and 120 mm Hg and, in doing so, utilized much of the contractile capacity of the muscle. A stretch-mediated, co-operative interaction between muscle cells has been put forward to explain these observations. Ear arteries from renal hypertensive rabbits differed from those of normotensive rabbits in having a higher NE threshold concentration and in constricting better against 140 mm Hg. They did so because of the mechanical advantage provided by a smaller internal radius and a thicker wall which reduced the load and stress placed on the muscle by the pressure. No muscle hyperplasia or hypertrophy was detected.

The kinetics of post-vibration tension recovery of the isolated rat portal vein.

1. The kinetics of post-vibration tension recovery have been examined during electrical, noradrenaline or KCl stimulation of the isolated rat portal vein. 2. Inhibition of isometric contractions produced by a combination of noradrenaline (20 microM) and KCl (53 mM) by longitudinal, 100 Hz sinusoidal vibration increased with increasing vibration amplitude up to a maximum of 78.7% of the active tension. This inhibition was little affected by a decrease in temperature from 37 to 25 degrees C. Recovery of tension after the end of vibration was complete and took place exponentially. The time constant for this recovery was little affected by changes in vibration amplitude, but increased from 1.72 +/- 0.09 to 4.35 +/- 0.33 sec, for large amplitude vibrations, when the temperature was lowered from 37 to 25 degrees C. 3. The increase in isometric tension during 50 Hz a.c. electrical field stimulation was exponential, apart from a minor initial activation component, and took place with a time constant of 1.25 +/- 0.17 sec. Neither delaying nor interrupting development of this contraction with inhibitory vibration altered the time constant for this exponential increase in tension. There was no correlation between the time constant and the maximum active tension achieved after vibration was stopped. 4. Post-vibration tension recovery during electrical, noradrenaline (20 microM) or KCl (120-130 mM) stimulation was independent of the nature of the stimulus at comparable times of stimulation, but the time constant increased during exposures of more than 10 sec to either noradrenaline or KCl. With noradrenaline, the increase was from 1.45 +/- 0.10 sec after 50 sec of stimulation to 2.24 +/- 0.16 sec after 336 sec of stimulation (P less than 0.0005). Such an increase in the time constant may reflect slower cycling of cross-bridges with an improvement in the efficiency by which contraction is maintained. 5. The kinetics of post-vibration tension recovery were those of a monomolecular or, as is more likely, a pseudo-monomolecular chemical reaction. A cross-bridge attachment model based on such a reaction has been used to interpret the observations.

Muscle load and constriction of the rabbit ear artery.

This isolated, perfused ear artery of the rabbit has been used to examine the effect of alterations in muscle load on the construction of arteries. The equilibrium muscle load, taken as the difference in wall stress between the relaxed and constricted artery at the same external radius, was varied by changing the transmural pressure and by constricting the artery. 2. The equilibrium muscle load increased initially and then declined with decreasing external radius when the transmural pressure was kept constant. The maximum muscle load was reached when the relaxed external radius had been reduced by 11% at 80 mmHg and by 4-5% (relative to the radius at 80 mmHg) at 160 mmHg. 3. Arteries from young rabbits (3-6 months in age) which were partially constricted by adrenaline or spontaneous activity responded better to 60 sec of 4 Hz field stimulation at transmural pressures above 100 mmHg than did relaxed arteries. Neither field stimulation nor high concentrations of noradrenaline ( is greater than 800 ng/ml.) were able to constrict most arteries effectively at pressures above 160-170 mmHg unless partial constriction was present. The partial constriction reduced the load placed on the muscle by the same transmural pressure. Constrictio n during field stimulation was due largely to the release of neurotransmitter. 4. Ear arteries from young and older rabbits differed little in their ability to constrict against different transmural pressures. The one major difference was a lesser maximum constriction of arteries from older rabbits (18-24 months in age). However, arteries from older rabbits constricted well at the higher transmural pressures only because wall thickening largely compensated for a decreased ability of the muscle to develop active tension. 5. It is concluded that a decrease in internal radius to wall thickness ratio by either sufficient partial vasoconstriction or by wall thickening favours constriction of arteries because the load placed on the muscle by the same transmural pressure is reduced. Wall thickening may be an important compensatory reaction for deteriorating muscle contraction.

The maintenance of arterial constriction at different transmural pressures.

1. Distensibility characteristics of the isolated, perfused rabbit ear artery were measured in the presence and absence of different concentrations of adrenaline.2. The major effect of varying the adrenaline concentration was to vary the radius at which active tension first developed. This radius was inversely related to the adrenaline concentration.3. Increases in radius of the constricted artery produced by pressures rising from 40 to 150 mm Hg were small relative to the increase in wall stress. Distension was opposed largely by increases in active tension. With some arteries (60%) an increase in pressure between 30 and 80 mm Hg was associated with a decrease in radius when low concentrations of adrenaline were present.4. The ability of the constricted ear artery to resist distension at transmural pressures of 100 mm Hg was uninfluenced by the adrenaline concentration provided constriction exceeded 28% of maximal. The static, incremental, circumferential modulus of the artery wall varied little from a value of 6.5 x 10(6) dyn/cm(2).5. The maximum active tension required to maintain constriction was inversely related to the degree of constriction and hence to the adrenaline concentration. The modulus for fully or near-fully activated muscle was 18.5 x 10(6) dyn/cm(2) of media.6. Muscle function deteriorated following exposure of constricted arteries to pressures sufficient to overwhelm the constriction.7. These observations may be explained by a negative feedback system where the contractile elements are arranged in parallel with a length sensor element whose setting is determined by the concentration of adrenaline. The length sensor may be the cell membrane. It is concluded that a radius increase may be a primary stimulus for blood flow auto-regulation.