INTERNAL DIVISION OF CAPILLARIES IN RAT SKELETAL-MUSCLE IN RESPONSE TO CHRONIC VASODILATOR TREATMENT WITH ALPHA(1)-ANTAGONIST PRAZOSIN

Chronic vasodilatation represents a stimulus for capillary growth asso ciated with increased luminal shear stress. We have examined the ultra structure of more than 2000 capillaries to establish whether the seque nce of angiogenesis in response to this stimulus is similar to that de scribed during development and under pathological circumstances. Admin istration of the eel-blocker prazosin to rats for 2 weeks led to a gre ater capillary length density in extensor hallucis proprius muscles wi thout any change in capillary tortuosity: J(v)(c,f)=262+/-54 compared with 350+/-17 mm(-2) control compared with prazosin (P<0.002). There w ere obvious signs of endothelial cell (EC) activation after prazosin t reatment, including an increased proportion of capillaries with rough endoplasmic reticulum, large cytoplasmic vacuoles, thickened endotheli um and an irregular luminal surface. Capillaries from control muscles had a maximum of three ECs in cross section, whereas four ECs were not ed in 0.8+0.5% of capillaries after 1 week (n.s.) and 2.5+/-0.9% after 2 weeks (P<0.01) of treatment. This could be due to elongation and/or migration of ECs, as cell proliferation has not been described at the se time points. There was also an increase in the proportion of capill aries having a narrow, slit-like lumen (1.7+/-0.8% of controls; 7.1+/- 1.9% at 1 week; 8.8+/-2.5% at 2 weeks; P<0.02), some of which were sma ller in size (less than 2 mu m diameter) than in controls (3-5 mu m) a nd/or ''seamless'', i.e. lacking EC junctions. These may represent new ly formed vessels. Focal discontinuity of the basement membrane and ab luminal EC processes were rarely seen, and capillary growth by ablumin al sprouting appeared to be very infrequent (less than 0.001% of profi les). Of more importance was growth starting from the luminal side. Si gnificantly more thin cytoplasmic processes were observed protruding i nto the lumen of capillaries after 1 week (47.5+/-6.2%, P<0.001) and 2 weeks of prazosin (34.2+/-5.5%, P<0.05) than in control vessels (16.7 +/-3.9%). Some of these traversed the entire lumen and connected with endothelium of the opposite side, probably involving membrane fusion, resulting in the appearance of a double lumen. Individual capillaries with a complete double lumen were observed after 2 weeks' prazosin but comparatively rarely, in only four out of six muscles. These findings indicate a pattern of luminal growth which is completely different fr om intussusceptive growth previously described during development, and from the abluminal capillary sprouting seen under pathological circum stances.