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 approximately 25 microns) 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 greater than 25 microns), arterioles (less than 25 microns), 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 microns. 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.

The hypothesis, based on in vitro experiments on large conduit arteries, that endothelium-derived nitric oxide is a mediator of vascular myogenic reactivity was tested in cat gastrocnemius muscle in vivo. This was done by comparing, in the absence and presence of effective endothelium-derived nitric oxide blockade by the specific inhibitors NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester, myogenic responses in defined consecutive vascular sections to dynamic vascular transmural pressure stimuli, to arterial occlusion (reactive hyperaemia), and to arterial pressure changes (autoregulation of blood flow and capillary pressure). The results demonstrated that the myogenic vascular reactivity to quick ramp transmural pressure stimuli was not attenuated by endothelium-derived nitric oxide blockade, but rather reinforced. The amplitude of the reactive hyperaemia response was unaffected by endothelium-derived nitric oxide blockade, but its duration was shortened because of faster myogenic constriction, especially of large-bore arterial resistance vessels greater than 25 microns, in the recovery phase. Both the improved myogenic responsiveness to transmural pressure stimuli and the shortening of the reactive hyperaemia by endothelium-derived nitric oxide blockade suggested that endothelium-derived nitric oxide released in vivo acts as a 'metabolic' factor which certainly does not improve, but rather depresses myogenic vascular reactivity. Autoregulation of blood flow and capillary pressure were well preserved in the presence of endothelium-derived nitric oxide blockade. It was concluded from the results of these multifaceted tests that myogenic vascular regulation in skeletal muscle in vivo seems independent of endothelium-derived nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)

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 reactive hyperaemia response cat skeletal muscle to 2-120 s arterial occlusions was analysed with regard to amplitude, duration, 'excess blood flow' and site of dilator action along the vascular bed. The last-mentioned was assessed with a new whole-organ technique permitting continuous segmental resistance recordings in arterial vessels greater than 25 microns, arterioles less than 25 microns and veins. Peak amplitude, duration and excess flow all increased with increasing occlusion length, of which excess flow was linearly related to occlusion length. The site of active dilatation was preferentially confined to arterioles less than 25 microns in which complete relaxation was observed after only 20 s occlusion, although the duration of the response continued to increase with more prolonged occlusions. A graded, but less pronounced, dilatation occurred in the arterial vessels greater than 25 microns and in the veins, the former exhibiting a 63% inhibition of tone as a maximum response at 120 s occlusion. The recovery phase was characterized by a vivid active constrictor component apparently protecting the capillaries from excessive pressure load upon arterial occlusion release, but this constriction became attenuated at long occlusions, thereby prolonging the hyperaemia response. The role of myogenic regulatory mechanisms in the responses was assessed from observed segmental resistance reactions to selectively applied transmural pressure stimuli similar to those elicited by arterial occlusion/release. It was concluded that myogenic mechanisms alone could explain the amplitude of the reactive hyperaemia response at short (up to 30 s) occlusions. Metabolic mechanisms seemed to be responsible for further relaxation of the proximal arterial vessels at longer occlusions, and also for the increased duration of the hyperaemia response at occlusions exceeding 10 s. Blockade of nitric oxide formation (endothelium-derived relaxing factor) did not seem to affect the reactive hyperaemia response.

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.