The aim of this study was to evaluate a possible humoral beta 2-adrenergic effect on the capillary pressure autoregulation capacity in cat skeletal muscle during bleeding. For this purpose capillary pressure autoregulation in response to graded decrease in arterial pressure was studied in sympathectomized muscle in the control state, and during haemorrhagic hypovolaemia in the presence and absence of selective beta 2-adrenoceptor blockade (ICI 118,551). The study was performed with a technique that permits continuous recordings of average capillary pressure in absolute terms and of the regional pre- and postcapillary vascular resistance, from which the pre- to post capillary resistance ratio could be determined. In the pre-haemorrhagic control state, an experimental decrease in arterial pressure from 100 to 50 mmHg caused a fall of capillary pressure from 17.6 by only 1.7 mmHg (delta PA/delta Pc = 29), demonstrating an efficient capillary pressure autoregulation. This autoregulation was accomplished by a decrease in pre- to post capillary resistance ratio in turn being a result of active precapillary dilatation and a passive increase in post capillary vascular resistance. Haemorrhage per se, via a humoral alpha-adrenergic preferentially precapillary vasoconstriction, caused a decrease in capillary pressure to 16.8 mmHg at arterial pressure 100 mmHg. A superimposed decrease in arterial pressure to 50 mmHg resulted in a capillary pressure fall by 3.7 mmHg (delta PA/delta Pc = 14), indicating impaired auto-regulation capacity. This attenuation to a great extent could be ascribed to adrenaline-induced B2-adrenoceptor stimulation, since beta 2-blockade restored the delta arterial pressure/capillary pressure ratio to 20. Low-dose isoprenaline infusion in the control state similarly caused marked impairment of capillary pressure autoregulation. The beta 2-adrenergic attenuation of capillary pressure autoregulation appears to be a beneficial effect in haemorrhagic hypotension, since it lowers capillary pressure passively in relation to the arterial pressure fall, thereby reinforcing the alpha-adrenergic active capillary pressure decrease, leading to more effective transcapillary fluid absorption and, hence, improved replenishment of plasma volume.

This study describes the integrated sympathetic/metabolic control of capillary pressure (Pc) and filtration in cat skeletal muscle as studied during graded exercise and superimposed graded (2, 6 and 16 Hz) vasoconstrictor nerve excitation. The applied technique permitted simultaneous analysis of the underlying changes of resistance in the whole vascular bed (RT) and in its large-bore arterial resistance vessels (greater than 25 microns), small arterioles (less than 25 microns) and veins. Graded exercise per se caused graded increases in capillary pressure, which at heavy work exceeded the resting control value by 12.2 mmHg, in turn leading to marked loss of plasma fluid by filtration. Sympathetic nerve stimulation was much more efficient in lowering capillary pressure during exercise than at rest, in spite of an exercise-induced marked attenuation of the vasoconstrictor response (RT). The sympathetically evoked capillary pressure fall per unit resistance increase was larger the greater the degree of exercise vasodilation, implying a highly nonlinear relation between capillary pressure and RT and also between the more direct determinant of capillary pressure the post- to precapillary resistance ratio, and RT. Strenuous exercise in vivo is known to be associated with a markedly increased reflex sympathetic discharge to exercising muscle which has been a puzzling feature in view of its untoward restriction of the exercise hyperaemia response. To the extent the present results are representative for this in vivo situation, they suggest that sympathetic discharge to exercising muscle, in spite of some flow restricting effect, might serve a highly beneficial function, causing effective protection against excessive work-induced rise of capillary pressure and harmful plasma fluid loss into the extravascular space of working muscle.

The relation between the capacitance response (regional blood volume mobilization) and the venous resistance response, i.e. the two main functions of the venous system, was investigated during graded sympathetic nerve excitation in cat gastrocnemius muscle under well defined experimental conditions. The neural capacitance response was also compared with the total regional vascular resistance response and its precapillary resistance component. A reliable distinction between precapillary and postcapillary resistance reactions was made possible by a whole-organ technique permitting continuous recordings of hydrostatic capillary pressure. In the control state, in which a transcapillary fluid equilibrium prevailed, total regional vascular resistance response, precapillary resistance component and venous resistance response averaged 16.6, 14.5 and 2.1 PRU, respectively and total regional blood volume was calculated to comprise 1.0 ml 100 g tissue-1. Graded sympathetic activation, causing graded increments in total regional vascular resistance response, precapillary resistance component and venous resistance response by maximum values of 96, 88 and 8 PRU respectively, were associated with graded decrease in total regional blood volume, at maximum by an average value of 0.57 ml 100 g tissue-1. The relations between regional blood volume mobilization on the one hand, and total regional vascular resistance response, precapillary resistance component and venous resistance response on the other, were all non-linear, implying that the sympathetic volume decrease per unit resistance increase was greater for small than large resistance increases.(ABSTRACT TRUNCATED AT 250 WORDS)

The sympathetic nervous control of the vascular bed of cat gastrocnemius muscle was studied with a new whole-organ technique which permits simultaneous, continuous and quantitative measurements of capillary pressure (Pc), capillary fluid exchange and resistance reactions in the whole vascular bed and in its three consecutive sections: large-bore arterial vessels (greater than 25 microns), arterioles (less than 25 microns) and veins. The results demonstrated a distinct neural control of all three consecutive vascular sections, graded in relation to the rate of nerve excitation up to maximum at 16 Hz. Stimulation at high rates, which in the steady state caused an average rise of overall regional resistance from 15.3 to 120 PRU (7.8-fold increase), thus raised large-bore arterial vessel resistance from 8.8 to 64 PRU (7.3-fold increase), arteriolar resistance from 4.5 to 49 PRU (10.9-fold increase) and venous resistance from 2.0 to 7 PRU (3.5-fold increase). The rate of resistance development (PRUs-1) of the sympathetic constrictor response was much higher in the arteriolar than in the other sections, which indicates that the neural control is especially prompt and efficient in the arterioles. A passive component was shown to contribute to the described responses only on the venous side, but in no case by more than 10% of the total sympathetic venous resistance response, which thus is mainly active. Of special functional importance was that the new technique provided information about the adrenergic control of Pc in absolute figures. From the control value of 19 mmHg, graded sympathetic stimulation caused a graded decline in Pc, at maximum constriction by about 7 mmHg. This resulted in marked net transcapillary fluid absorption, in turn increasing plasma volume.

An attempt was made to assess, from a large sample (n = 567), the normal level of hydrostatic capillary pressure (Pc) in resting skeletal muscle and the extent of Pc regulation as effected by strictly graded activation of metabolic and adrenergic control mechanisms over the entire physiological range of vascular tone. With the use of a new whole-organ technique, Pc towards the venous end of the capillary was continuously recorded at constant arterial pressure (100 mmHg) and under simultaneous observations of total regional vascular resistance (RT), precapillary resistance (Ra) and post-capillary resistance (RV). In the control state with a Starling fluid equilibrium, a venous pressure of 7 mmHg and normal vascular tone (RT = 19.1 +/- 0.3 PRU), Pc averaged 16.7 +/- 0.3 mmHg. Graded metabolic dilatation (muscle exercise), decreasing RT to a minimum value of 1.7 PRU, caused progressive increase in Pc up to 32 mmHg and consequent fluid filtration. Conversely, graded adrenergic constriction, increasing RT to a maximum of 100 PRU, caused a progressive decrease in Pc down to 10 mmHg and consequent fluid absorption. The relation between Pc and RT was highly non-linear, Pc increasing more steeply the more RT approached low values, and was described by the power function: Pc = 36.43 x RT-0.27 (r = -0.79, P less than 0.001). The resistance ratio, Rv/Ra (the main determinant of Pc), and vascular tone (RT) showed a similar non-linear relation. Regulatory change of Rv/Ra was mainly accomplished by active change of Ra, but a pronounced Rv decrease (venodilatation) occurred in the lowest RT range, exerting a protective function against excessive increase in Pc and detrimental plasma fluid loss.

The metabolic control of the vascular bed in cat gastrocnemius muscle during exercise was studied with a new technique (Björnberg et al. 1988) permitting continuous and simultaneous recordings of arteriolar and capillary pressures, and of resistances in the following consecutive vascular section: proximal arterial resistance vessels greater than 25 microns, arterioles less than 25 microns, and on the venous side. The study thereby provided quantitative data for resistance and active intrinsic tone in these vascular segments at rest, during graded exercise vasodilatation, and in the post-exercise period. Slight activation of the metabolic control system by low-frequency somatomotor nerve stimulation ('light exercise') caused inhibition of intrinsic tone and decreased vascular resistance selectively in the arteriolar section. At increasing workloads, arteriolar resistance was further decreased, but resistance and tone in the proximal arterial resistance vessels and the veins then became clearly reduced as well. This difference in effectiveness of the metabolic control system on the different segments of the vascular bed was expressed quantitatively in terms of a 'metabolic vasodilator index'. Graded activation of the metabolic control system led to a marked segmental redistribution of intrinsic vascular tone, in turn resulting in an increased pressure drop across the proximal arterial vessels in the veins and a decreased pressure drop over the arterioles. The observed decrease in the pre- to post-capillary resistance ratio caused, at a constant arterial pressure of 100 mmHg, a graded increase in capillary pressure with increasing workloads, at maximum vasodilatation by an average value of 14 mmHg above the resting control value of 15.4 +/- 0.6 mmHg. In the post-exercise period, recovery of vascular tone to control was more rapid in the proximal arterial resistance vessels and the veins than in the arteriolar segment.

An arterial and venous microcannulation technique was developed for circulatory studies in the cat gastrocnemius muscle which, based on detailed morphological and functional observations of the microvascular arrangement, seems to permit continuous recordings of pressure in arterioles (diameter ± 25 μm) and capillary pressure. These variables in combination with measurements of arterial and venous pressure and blood flow provided a means of continuous simultaneous recordings of total as well as segmental resistances in defined sections of the vascular bed, viz. in large arterial vessels (diameter ± 25 μm), arterioles (± 25 μm), and on the venous side. This new technique was applied to a study of the site(s) of autoregulatory reactions along the vascular bed evoked by changes of arterial pressure over the range 50–150 mmHg. The results indicated that active autoregulation mainly occurred within arterioles smaller than about 25 μm. In larger arterial vessels concomitant moderate active smooth muscle adjustments barely balanced out the pressure‐induced passive calibre changes, and the venous vessels did not seem to contribute actively to autoregulation, but exhibited a passive change in postcapillary resistance (Rven). The described pattern of response results in quite effective autoregulation of blood flow and capillary pressure (PC). The observed passive Rven change, via its effect on the pre‐ to postcapillary resistance ratio, seems to explain the fact that autoregulation of Pc can be more efficient than flow autoregulation. The study also provided quantitative data for the level of active intrinsic vascular tone in defined consecutive sections of the muscle vascular bed at normal arterial pressure and for segmental redistributions of tone evoked by pressure alterations.

A venous microcannulation technique applied to the cat gastrocnemius muscle was developed which, based on morphological and functional demonstrations of anastomotic connections between two supplying segmental vascular circuits at the level of capillaries and/or post-capillary venules, seems to permit continuous recordings of hydrostatic pressure (denoted Pcvenule) transmitted from such anastomoses, that is, from a site close to the main fluid exchange vessels. For validity tests, such Pcvenule recordings were compared with simultaneous estimates of capillary pressure (Pc) with the isogravimetric technique (Pciso) and, further, with data for experimentally evoked changes of Pc derived from volumetric recordings of net transvascular fluid flux divided by the capillary filtration coefficient (delta Pcvol). Simultaneously obtained data for Pcvenule and Pciso showed close agreement, and the Pcvenule and Pcvol data showed a highly significant linear correlation over a wide range of Pc changes. These results indicate that reliable estimates of Pc can be obtained with the Pcvenule method. It allows for continuous Pc recordings without interfering with normal vascular reactivity and can be applied to non-isogravimetric conditions and combined with simultaneous observations of whole-organ transvascular fluid exchange. At normal arterial and venous pressures and vascular tone, Pcvenule averaged 16.2 +/- 0.2 mm Hg, at which a Starling fluid equilibrium prevailed, and increased with decreasing vascular tone, resulting in net transvascular fluid filtration.

The controversial hypothesis that capillary pressure (Pc) is autoregulated in response to arterial pressure (PA) alterations was tested in sympathectomized cat skeletal muscle by studying the relation between Pc and PA under conditions of well preserved vascular tone and reactivity, during papaverine-induced maximal vasodilatation (passive vascular bed), and during impaired vascular reactivity caused by preparatory surgery, or by low dose isoproterenol administration. The latter states resembled such under which Pc autoregulation unintentionally seems to have been studied previously. Capillary pressure was assessed with the Pcvenule method for continuous direct pressure recordings from capillaries/postcapillary venules (Mellander et al. 1987) and simultaneously derived from observed net transvascular fluid flux divided by CFC. Resistances in the whole vascular bed and in its pre- and postcapillary segments (Ra and Rv) were determined from recordings of blood flow, PA, Pc, and PV. During preserved vascular reactivity, Pc was found to be virtually constant, that is, almost perfectly autoregulated, over the PA range from 50 to 180 mmHg, whereas in the passive vascular bed there was a direct linear relation between Pc and PA (y = 0.137x + 11.69; r = 0.97). The delta Pc/delta PA ratio was about 1/70 in the normal reactive, and 1/7 in the passive, vascular bed, implying an increase in Pc by 1 mmHg for every 70 mmHg and every 7 mmHg increase in PA, respectively. Capillary pressure autoregulation was explained by precise adjustments of Ra/Rv in relation to PA elicited by myogenic and metabolic regulatory mechanisms. This protective reaction against plasma loss during increased PA was abolished during maximal vasodilation, and was much impaired by surgical trauma, partly via a beta-adrenergic inhibitory effect, and by isoproterenol, in turn causing gross transcapillary fluid fluxes. The latter findings might explain failing Pc autoregulation in some previous studies undertaken under seemingly similar conditions.