Effect of pikamilon on the cortical blood supply and microcirculation in the pial arteriole system

Pikamilon was shown to increase blood supply in cerebral cortex in conscious rats and rabbits. The increase in blood flow has been revealed under intravenous, intraperitoneal and systemic administration of the drug. There is a pronounced dilatation of pial arterioles under pikamilon action while applied locally. Most dilation occurs in arterioles with the initial diameter of 10-20 microns. With the increase of pial arterioles diameter, dilatory effect of pikamilon, is reduced.     

Temporal effect of alcohol consumption on reactivity of pial arterioles: role of oxygen radicals

Chronic alcohol consumption reduces nitric oxide synthase-dependent responses of pial arterioles via mechanisms that remain uncertain. In addition, the temporal effects of alcohol on pial arterioles is unclear. Thus our goals were to examine the role of oxygen-derived free radicals in alcohol-induced impairment of cerebrovascular reactivity and the temporal effect of alcohol on reactivity of pial arterioles. Sprague-Dawley rats were pair-fed a liquid diet with or without alcohol for 2-3 wk, 2-3 mo, or 5-6 mo. We measured the in vivo diameter of pial arterioles in response to nitric oxide synthase-dependent dilators acetylcholine and ADP and the nitric oxide synthase-independent dilator nitroglycerin. In nonalcohol-fed rats, acetylcholine (1.0 and 10 microM) and ADP (10 and 100 microM) produced dose-related dilatation of pial arterioles. Whereas there was no difference in reactivity of arterioles to the agonists in rats fed the nonalcohol and alcohol diets for a period of 2-3 wk, there was a significant impairment in reactivity of arterioles to acetylcholine and ADP, but not nitroglycerin, in rats fed the alcohol diet for longer durations. We then found that treatment with superoxide dismutase did not alter baseline diameter of pial arterioles in nonalcohol-fed or alcohol-fed rats, but significantly improved impaired nitric oxide synthase-dependent dilatation of pial arterioles in alcohol-fed rats. Thus our findings suggest a temporal relationship in the effects of alcohol on reactivity of pial arterioles and that impaired nitric oxide synthase-dependent cerebral vasodilatation during chronic alcohol consumption may be related, in part, to enhanced release of oxygen-derived free radicals.     

Changes in the reactivity of microvessels of the pia mater system of rats during ontogenesis

Changes in microvascular reactivity in pia mater system have been studied under conditions of bilateral occlusion of common carotid arteries in rats of different age groups. The studies were performed on the 7th, 30th, 45th and 90th day of the postnatal development. The occlusion of common carotid arteries lasted 6 min in week-old animals and 9 min in rats of other age groups. The phase character of microvascular reactivity has been determined. It has been found that dilation of arterioles depends on the age of the animal. So dilation of precortical arterioles averaged 20-25% of the initial level in 7-day-old animals and increased to 60-75% in 30- and 45-day-old animals. It has been determined that the smaller is the diameter of the vessels the more expressed is their reactivity. It has been shown that a steady reaction of compensatory adaptation in microvessels in characteristic only of adult animals.     

Impairment of nitric oxide synthase-dependent dilatation of cerebral arterioles during infusion of nicotine

The effects of nicotine on nitric oxide synthase (NOS)-dependent reactivity of cerebral arterioles remain uncertain. Our first goal was to examine whether infusion of nicotine alters NOS-dependent reactivity of cerebral arterioles. Our second goal was to examine the mechanisms that may account for the effects of nicotine on cerebral arterioles. We measured the diameter of pial arterioles to NOS-dependent (ADP and acetylcholine) and NOS-independent (nitroglycerin) agonists before and after the infusion of nicotine (2 microg x kg(-1) x min(-1) iv for 30 min, followed by a maintenance dose of 0.35 microg x kg(-1) x min(-1)). ADP- and acetylcholine-induced vasodilatation was impaired after the infusion of nicotine. In contrast, nicotine did not alter vasodilatation to nitroglycerin. Next, we examined whether the impaired responses of pial arterioles during infusion of nicotine may be related to oxygen radicals. We found that application of superoxide dismutase or tetrahydrobiopterin during infusion of nicotine could prevent impaired NOS-dependent vasodilatation. Thus acute exposure of cerebral vessels to nicotine specifically impairs NOS-dependent dilatation via the production of oxygen radicals possibly related to an alteration in the utilization of tetrahydrobiopterin.     

Acute infusion of nicotine impairs nNOS-dependent reactivity of cerebral arterioles via an increase in oxidative stress.

Our goals were to determine whether acute exposure to nicotine alters neuronal nitric oxide synthase (nNOS)-dependent reactivity of cerebral arterioles and to identify a potential role for oxidative stress in nicotine-induced impairment in nNOS-dependent responses of cerebral arterioles. We measured in vivo diameter of cerebral arterioles to nNOS-dependent (N-methyl-d-aspartate and kainate) and -independent (nitroglycerin) agonists before and during acute treatment with nicotine. We found that nNOS-dependent, but not -independent, vasodilatation was impaired during treatment with nicotine. In addition, treatment of the cerebral microcirculation with tempol (1 h before infusion of nicotine) prevented nicotine-induced impairment in nNOS-dependent vasodilatation. Furthermore, the production of superoxide anion (lucigenin chemiluminescence) was increased in parietal cortex tissue of rats by treatment with nicotine, and this increase in superoxide anion production could be inhibited by tempol. Our findings suggest that acute exposure to nicotine impairs nNOS-dependent dilatation of cerebral arterioles by a mechanism that appears to be related to the formation of superoxide anion.     

Chronic exposure to nicotine alters endothelium-dependent arteriolar dilatation: effect of superoxide dismutase.

The first goal of this study was to determine whether chronic injection of nicotine alters endothelium-dependent arteriolar dilatation. We measured the diameter of cheek pouch resistance arterioles (approximately 50 microm in diameter) in response to endothelium-dependent (acetylcholine and ADP) and -independent (nitroglycerin) agonists in control hamsters and hamsters treated with nicotine (2 microg. kg-1. day-1 for 2-3 wk). In control hamsters, acetylcholine (0.1 and 1.0 microM) dilated arterioles by 13 +/- 2 and 31 +/- 3%, respectively, and ADP (1.0 and 10 microM) dilated arterioles by 18 +/- 1 and 30 +/- 1%, respectively. In contrast, acetylcholine (0.1 and 1.0 microM) dilated arterioles by only 5 +/- 2 and 12 +/- 3%, respectively, and ADP (1.0 and 10 microM) dilated arterioles by only 7 +/- 2 and 13 +/- 3%, respectively, in animals treated with nicotine (P < 0.05 vs. response in control hamsters). Nitroglycerin produced similar dose-related dilatation of cheek pouch arterioles in control and nicotine-treated hamsters. Our second goal was to examine a possible mechanism for impaired endothelium-dependent arteriolar dilatation during chronic treatment with nicotine. We found that superfusion of the cheek pouch microcirculation with superoxide dismutase (150 U/ml) restored impaired endothelium-dependent, but did not alter endothelium-independent, arteriolar dilatation in hamsters treated with nicotine. Superfusion with superoxide dismutase did not alter endothelium-dependent or -independent arteriolar dilatation in control hamsters. We suggest that chronic exposure to nicotine produces selective impairment of endothelium-dependent arteriolar dilatation via a mechanism related to the synthesis/release of oxygen-derived free radicals.     

Biological effects of exposure to high frequency electromagnetics on rabbits and guinea pigs]

To investigate the biological effects of exposure to feeble high frequency electromagnetism, skin surface temperature, blood vessel (arterioles and venules) diameter were examined, using infrared thermography, a laser doppler flowmeter, and a video microscope, respectively, in the ear of rabbits. After exposing the ear of rabbits to high frequency electromagnetism value of 9 MHz for 15 minutes, continued rising of local temperature was demonstrated. Though dilatation of arterioles was not seen. In addition, venules tended to dilate and blood flow also to increase, and microcirculation was accelerated at the site where electromagnetism was exposed. Hazardous effects of long term exposures of high frequency electromagnetism (9 MHz for 30 days, 8 hours/day) on guinea pigs were not observed in their behavior, food consumption, body and organ weights, hematological and biochemical values, macroscopic and microscopic findings on autopsy.     

Effect of cigarette smoke extract on arteriolar dilatation in vivo

Mayhan, William G., and Glenda M. Sharpe. Effect ofcigarette smoke extract on arteriolar dilatation in vivo.J. Appl. Physiol. 81(5):1996-2003, 1996.The goal of this study was to determine whethercigarette smoke extract alters dilatation of arterioles in vivo inresponse to agonists that produce activation of ATP-sensitive potassiumchannels and activation of adenylate cyclase. By using intravitalmicroscopy, we measured diameter of arterioles contained within themicrocirculation of the hamster cheek pouch during suffusion withagonists in the absence and presence of cigarette smoke extract (0.1, 0.5, and 1.0%). Before treatment with cigarette smoke extract,activation of ATP-sensitive potassium channels with aprikalim andcromakalim produced dose-related dilatation of cheek poucharterioles. Similarly, activation of adenylate cyclasewith isoproterenol and forskolin produced dose-related dilatation ofcheek pouch arterioles before treatment with cigarette smoke extract.Superfusion of 0.1% cigarette smoke extract did not change baselinediameter of arterioles and did not alter responses of cheek poucharterioles to activation of ATP-sensitive potassium channels andadenylate cyclase. Superfusion of 0.5 and 1.0% cigarette smoke extractalso did not alter baseline diameter of arterioles but did impairdilatation of arterioles in response to activation of ATP-sensitivepotassium channels and adenylate cyclase. These findings suggest thatcigarette smoke extract impairs dilatation of resistance arterioles inresponse to activation of important cellular dilator pathways.

     

Remodeling of the skeletal muscle microcirculation increases resistance to perfusion in obese Zucker rats

Whereas previous studies have demonstrated that the development of syndrome X in obese Zucker rats (OZR) is associated with impaired arteriolar reactivity to vasoactive stimuli, additional results from these studies indicate that the passive diameter of skeletal muscle arterioles is reduced in OZR versus lean Zucker rats (LZR). On the basis of these prior observations, the present study evaluated structural alterations to the skeletal muscle microcirculation as potential contributors to an elevated vascular resistance. Isolated skeletal muscle resistance arterioles exhibited a reduced passive diameter at all levels of intralumenal pressure and a left-shifted stress-strain curve in OZR versus LZR, indicative of structural remodeling of individual arterioles. Histological analyses using Griffonia simplicifolia I lectin-stained sections of skeletal muscle demonstrated reduced microvessel density (rarefaction) in OZR versus LZR, suggesting remodeling of entire microvascular networks. Finally, under maximally dilated conditions, constant flow-perfused skeletal muscle of OZR exhibited significant elevations in perfusion pressure versus LZR, indicative of an increased resistance to perfusion within the microcirculation. These data suggest that developing structural alterations to the skeletal muscle microcirculation in OZR result in elevated vascular resistance, which may, acting in concert with impaired arteriolar reactivity, contribute to blunted active hyperemic responses and compromised performance of in situ skeletal muscle with elevated metabolic demand.     

Inhibition of NADPH oxidase improves impaired reactivity of pial arterioles during chronic exposure to nicotine.

Our goals were to determine whether chronic exposure to nicotine alters nitric oxide synthase (NOS)-dependent reactivity of cerebral (pial) arterioles and to identify a potential role for NADPH oxidase in impaired NOS-dependent responses during chronic exposure to nicotine. We measured in vivo diameter of pial arterioles to NOS-dependent (acetylcholine and ADP) and -independent (nitroglycerin) agonists in saline-treated rats and rats chronically treated with nicotine (2 mg.kg(-1).day(-1) for 2 wk via an osmotic minipump). We found that NOS-dependent, but not -independent, vasodilatation was impaired in nicotine-treated compared with saline-treated rats. In addition, the production of superoxide anion (lucigenin chemiluminescence) was increased in rats treated with nicotine compared with saline-treated rats. Furthermore, using Western blot analysis, we found that chronic exposure to nicotine increased p47phox protein in the parietal cortex. Finally, we found that apocynin (40 mg.kg(-1).day(-1)) in the drinking water to inhibit NADPH oxidase alleviated impaired NOS-dependent cerebral vasodilatation in nicotine treated rats but did not alter NOS-dependent responses in saline treated rats and did not alter NOS-independent reactivity in saline- or nicotine-treated rats. These findings suggest that chronic exposure to nicotine impairs NOS-dependent dilatation of pial arterioles by a mechanism that appears to be related to the formation of superoxide anion via activation of NADPH oxidase.     

COX-2-dependent delayed dilatation of cerebral arterioles in response to bradykinin

Bradykinin (BK) is released in the brain during injury and inflammation. Activation of endothelial BK receptors produces acute dilatation of cerebral arterioles that is mediated by reactive oxygen species (ROS). ROS can also modulate gene expression, including expression of the inducible isoform of cyclooxygenase (COX-2). We hypothesized that exposure of the brain to BK would produce acute dilatation, which would be followed by a delayed dilatation mediated by COX-2. To test this hypothesis in anesthetized rats, BK was placed twice in cranial windows for 7 min, after which the windows were flushed to remove residual BK. The two BK exposures were separated by 30 min. Each BK exposure produced acute dilatation of cerebral arterioles, after which diameter rapidly returned to baseline. Over the subsequent 4.5 h after the second BK exposure, arterioles dilated 48 +/- 8%. Treatment of the cranial window with NS-398, a selective COX-2 inhibitor, or dexamethasone, significantly attenuated the delayed dilatation. Aminoguanidine, a selective inhibitor of inducible nitric oxide synthase, did not alter the delayed dilatation. Cotreatment of cranial windows with BK, superoxide dismutase, and catalase also prevented the delayed dilatation. In separate experiments, exposure of the cortical surface to BK upregulated leptomeningeal expression of COX-2 mRNA. Our results suggest that acute, time-limited exposure of the brain to BK produces delayed dilatation of cerebral arterioles dependent on expression and activity of COX-2.     

Augmented adrenergic vasoconstriction in hypertensive diabetic obese Zucker rats

This study examined skeletal muscle microvessel reactivity to constrictor stimuli in obese (OZR) versus lean Zucker rats (LZR). Gracilis arteries from both rat groups were isolated, cannulated with glass micropipettes, and viewed via television microscopy. Changes in vessel diameter were measured with a video micrometer. Arterial constriction to norepinephrine was elevated in OZR versus LZR, although vasoconstrictor reactivity to endothelin and angiotensin II was unaltered. Differences in reactivity between vessels of LZR and OZR were not explained by the loss of either endothelial nitric oxide synthase or beta-adrenergic receptor function. Reactivity of in situ cremasteric arterioles of OZR to norepinephrine was elevated versus LZR. Treatment with prazosin increased the diameter of in vivo gracilis arteries of OZR to levels determined in LZR and also normalized blood pressure in OZR. These results suggest that the constrictor reactivity of skeletal muscle microvessels in OZR is heightened in response to alpha-adrenergic stimuli and that development of diabetes in OZR may be associated with impaired skeletal muscle perfusion and hypertension due to microvessel hyperreactivity in response to sympathetic stimulation.     

Cytokines and vascular reactivity in resistance arteries

Cytokine levels are elevated in many cardiovascular diseases and seem to be implicated in the associated disturbances in vascular reactivity reported in these diseases. Arterial blood pressure is maintained within a normal range by changes in peripheral resistance and cardiac output. Peripheral resistance is mainly determined by small resistance arteries and arterioles. This review focuses on the effects of cytokines, mainly TNF-alpha, IL-1beta, and IL-6, on the reactivity of resistance arteries. The vascular effects of cytokines depend on the balance between the vasoactive mediators released under their influence in the different vascular beds. Cytokines may induce a vasodilatation and hyporesponsiveness to vasoconstrictors that may be relevant to the pathogenesis of septic shock. Cytokines may also induce vasoconstriction or increase the response to vasoconstrictor agents and impair endothelium-dependent vasodilatation. These effects may help predispose to vessel spasm, thrombosis, and atherogenesis and reinforce the link between inflammation and vascular disease.     

Static magnetic fields alter arteriolar tone in vivo

This study was designed to directly quantify the effect of localized static magnetic field (SMF) exposure on the diameter of microvessels in adult rat skeletal muscle in vivo. Microvascular networks in the exteriorized rat spinotrapezius microvasculature were exposed to a localized, uniform 70 mT SMF for 15 min. Arteriolar vessel diameters were measured; and the extent of vessel contraction, microvascular tone, was calculated before exposure, immediately after exposure, and 15 and 30 min after removal of the field. A calculated value of high tone corresponds to vessels that are vasoconstricted and a calculated value of low tone refers to vessels that are vasodilated. Vessels with initial tone <15% showed an increasing trend in tone and, conversely, vessels with initial tone >15% showed a significant (P < 0.05) decrease in tone 15 and 30 min following application, respectively. Further classification of the data with regards to the initial vessel diameter demonstrated that vessels with initial diameters <30 microm and initial tone <15%, smaller diameter vessels that are initially vasodilated, showed significant (P < 0.05) increase in tone immediately, 15 and 30 min following SMF exposure. Additionally, <30 microm vessels with >15% initial tone, smaller diameter vessels that are initially vasoconstricted, demonstrated a significant (P < 0.05) decrease in tone 30 min after SMF exposure. Vessels with initial diameters >30 microm had no significant response to the SMF. These results imply that SMF exposure influences arteriolar diameters, and therefore microvascular tone, in a restorative fashion acting to normalize the tone to the median tone value of 15% following exposure. Because this response occurs primarily in the resistance arterioles, which significantly influence tissue perfusion, SMF application could be efficacious for the treatment of both ischemic and edematous tissue disorders involving compromised microvascular function.     

Temporal and spatial variations of cell-free layer width in arterioles

Separation of red blood cells and plasma in microcirculatory vessels produces a cell-free layer at the wall. This layer may be an important determinant of blood viscosity and wall shear stress in arterioles, where most of the hydraulic pressure loss in the circulatory system occurs and flow regulatory mechanisms are prominent. With the use of a newly developed method, the width of the cell-free layer was rapidly and repeatedly determined in arterioles (10- to 50-microm inner diameter) in the rat cremaster muscle at normal arterial pressure. The temporal variation of the cell-free layer width was non-Gaussian, but calculated mean and median values differed by <0.2 microm. The correlation length of the temporal variations downstream (an indication of mixing) was approximately 30 microm and was independent of pseudoshear rate (ratio of mean velocity to vessel diameter) and of vessel diameter. The cell-free layer width was significantly different on opposite sides of the vessel and inversely related. Increasing red blood cell aggregability reduced this inverse relation but had no effect on correlation length. In the diameter range studied, the mean width of the cell-free layer increased from 0.8 to 3.1 microm and temporal variations increased from 30% to 70% of the mean width. Increased aggregability did not alter either relationship. In summary, the cell-free layer width in arterioles is diameter dependent and shows substantial non-Gaussian temporal variations. The temporal variations increase as diameter increases and are inversely related on opposite sides of the vessel.     

Superoxide dismutase restores endothelium-dependent arteriolar dilatation during acute infusion of nicotine

We previouslyshowed [Am. J. Physiol. 272 (Heart Circ. Physiol. 41):H2337-H2342, 1997] that nicotine impairsendothelium-dependent arteriolar dilatation. However, mechanisms thataccounted for the effect of nicotine on endothelium-dependentvasodilatation were not examined. Thus the goal of this study was toexamine the role of oxygen radicals in nicotine-induced impairment of arteriolar reactivity. We measured diameter of cheek pouch resistance arterioles (~50 µm diameter) in response to endothelium-dependent (ACh and ADP) and -independent (nitroglycerin) agonists before andafter infusion of vehicle or nicotine in the absence or presence ofsuperoxide dismutase. ACh, ADP, and nitroglycerin produced dose-relateddilatation of cheek pouch arterioles before infusion of vehicle ornicotine. Infusion of vehicle, in the absence or presence of superoxidedismutase (150 U/ml), did not alter endothelium-dependent or-independent arteriolar dilatation. In contrast, infusion of nicotine(2 µg · kg¹ · min¹)impaired endothelium-dependent, but not -independent, arteriolar dilatation. In addition, the effect of nicotine onendothelium-dependent vasodilatation was reversed by topicalapplication of superoxide dismutase. We suggest that nicotine impairsendothelium-dependent arteriolar dilatation via an increase in thesynthesis/release of oxygen-derived free radicals.

     

Network thermodynamic analysis of vasomotion in a microvascular network.

The modulation of microvascular blood flow by vasomotion in the individual vessels of a simple vascular network was simulated by means of a network thermodynamic model. The flow is driven under a pulsating pressure through two arcades of branching vasoactive arterioles into a passive resistance representing the capillary and venular beds. Each vessel was assumed to have the capability of decreasing rhythmically the local diameter over a short section by a specified fraction of the maximum value and to change the average diameter along its total length in response to alterations in intraluminal pressure. Blood was assumed to exhibit a simple linear viscous flow resistance. Alterations in flow rate and distribution through the network were determined as a function of the magnitude and frequency of vasomotion within the individual arterioles supplying blood to the microvascular bed. Specific cases are shown to illustrate how blood flow can be influenced by the patterns of vasomotion within the network.     

Impaired nitric oxide synthase-dependent dilatation of cerebral arterioles in type II diabetic rats

The goals of this study were to determine the effects of type II diabetes mellitus on nitric oxide synthase-dependent responses of cerebral arterioles and on endothelial nitric oxide synthase (eNOS) protein in cerebral arterioles. We examined dilatation of cerebral (pial) arterioles in 13-15 week old male lean and diabetic obese Zucker rats in response to nitric oxide synthase-dependent agonists (acetylcholine and adenosine diphosphate (ADP)) and a nitric oxide synthase-independent agonist (nitroglycerin). We found that acetylcholine (10 microM) increased cerebral arteriolar diameter by 10 +/- 3% (mean +/- SE) in lean Zucker rats, but by only 2 +/- 2% in diabetic obese Zucker rats (p<0.05). In addition, ADP (100 microM) increased cerebral arteriolar diameter by 20 +/- 2% in lean Zucker rats, but by only 8 +/- 2% in diabetic obese Zucker rats (p<0.05). In contrast, nitroglycerin produced similar vasodilatation in lean and diabetic obese Zucker rats. Thus, impaired dilatation of cerebral arterioles in diabetic obese Zucker rats is not related to non-specific impairment of vasodilatation. Following these functional studies, we harvested cerebral microvessels for Western blot analysis of eNOS protein. We found that eNOS protein was significantly higher in diabetic obese Zucker rats than in lean Zucker rats (p<0.05). Thus, type II diabetes mellitus impairs nitric oxide synthase-dependent responses of cerebral arterioles. In addition, eNOS protein from cerebral blood vessels is increased in diabetic obese Zucker rats.     

Ultrastructure of arterioles in the cat brain

Summary A total of 110 arterioles were examined in the brains of cats; different sites were studied including the cortex, putamen, pons and crus cerebri. No internal elastic laminae were seen in the subendothelial space, although occasional fragments of elastic material were present in the larger arterioles. The media was composed of one, two or three layers of smooth muscle cells which interlocked in such a way that the vessel wall thickness was constant. Numerous tight junctions were seen between adjacent smooth muscle cells and between the endothelium and smooth muscle cells. Apart from the usual cell organelles, the smooth muscle cells of arterioles had numerous dense patches on the cell surface. The structure of the adventitia varied according to the diameter of the vessel and the site in the brain; it contained adventitial cells, bundles of collagen fibres and nerve fibres. Innervation of arterioles was more constant in the brain stem than in the cortex. Metarterioles had less specialised, atypical smooth muscle cells, a discontinuous media and numerous, extensive myoendothelial tight junctions; they were not innervated by nerve fibres. The diameter of metarterioles was less than 10 m whereas that of arterioles was 10–45 m. The possible functional aspects of arteriolar innervation are discussed.     

Differentiation of blood vessels in the adipose tissue of lean and obese fetal pigs, studied by differential enzyme histochemistry

Subcutaneous adipose tissue was obtained from fetuses removed from pregnant obese (Ossabaw) and lean (crossbred) sows at three stages of gestation (70, 90, and 110 days). Histochemical analysis for nucleo-side phosphatase (NPase), alkaline phosphatase (APase), and NADH tetrazoleum reductase (NADH-TR) was conducted on fresh-frozen cryostat sections. Age- associated changes in NPase and NADH-TR reactions in the arteriolar system were correlated with the morphological development of the medial layer of arterioles and arteries. For instance, a strong NPase reaction in small arterioles was associated temporally with the assumption of a normal smooth muscle cell morphology and arrangement in the medial layer. In the youngest fetuses, strong NADH-TR reactions were only evident in small and presumptive arterioles and venules (associated with fat cells). Little NADH-TR reactivity was evident in larger arterioles and venules in 70-day tissue. Arteries and large arterioles were distinguished from veins and venules (strong reactions vs. weak reactions) with NADH-TR and NPase reactions in the oldest fetuses. In the younger fetuses, the NPase distinction (arterioles vs. veinules) was obvious before NADH-TR distinction. Small adipocyte-associated vessels were APase positive in the youngest fetuses, but APase reactivity was limited to short segments of vessel between arterioles and capillaries in the oldest fetuses. With the following exceptions, all the above observations were independent of fetal strain. In obese fetuses (110 day) small venules and small arterioles were equally reactive for NPase activity. Capillaries in obese fetuses (110 day) were NADH-TR reactive, whereas no activity was evident in capillaries from lean fetuses (110 day).(ABSTRACT TRUNCATED AT 250 WORDS)