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Biomedical subjects

P D Harris

Publications and source records attributed to P D Harris.

At least 19 recordsLinked to original sources
PubMed1992

Serotonin-induced dilation of small arterioles is not mediated via endothelium-derived relaxing factor in skeletal muscle.

Serotonin (5-HT) dilates precapillary arterioles in skeletal muscle. The purpose of this study was to determine if 5-HT releases endothelium-derived relaxing factor (EDRF) in this tissue. Diameters of third-order arterioles (A3) in the cremaster muscle of pentobarbital-anesthetized rats were measured via videomicroscopy. Concentration-response curves for acetylcholine, nitroprusside and 5-HT were obtained before and after the application of either hydroquinone (5 x 10(-4) M) or NG-nitro-L-arginine (10(-4) M). The involvement of prostaglandins was eliminated by ibuprofen (10(-4) M). In one group, 5-HT (20 micrograms/kg) and NG-nitro-L-arginine were given i.v. (30 mg/kg). The non-EDRF-dependent vasodilator papaverine (10(-5) M) was applied at the end of the protocol to determine the maximal resting diameter. When applied topically, both hydroquinone and NG-nitro-L-arginine significantly inhibited the dilation induced by acetylcholine, but neither agent affected the dilation to nitroprusside or 5-HT. NG-Nitro-L-arginine (i.v.) attenuated acetylcholine-induced dilation but not the dilation to intravenous 5-HT. These data suggest that 5-HT-induced dilation of small arterioles in skeletal muscle is EDRF-independent.

Acetylcholine↗
PubMed1992

EDRF as a possible mediator of sepsis-induced arteriolar dilation in skeletal muscle.

Vascular endothelial cells influence microvessel diameters in vivo and in vitro and participate in host-defense mechanisms during sepsis. We examined whether small arteriole dilation in skeletal muscle during high cardiac output bacteremia (HOB) and low cardiac output live Escherichia coli sepsis (LOS) is mediated by an endothelium-derived relaxing factor (EDRF). Local chemical blockade of EDRF by hydroquinone (HQ) substantially blunted acetylcholine-induced dilation of small arterioles. HQ also prevented large arteriole (55-135 microns) constriction and small arteriole (6-22 microns) dilation in the cremaster muscle of rats during HOB. In LOS, small arteriole dilation was also prevented by HQ but only during the early period when blood pressure was unchanged from baseline. HQ did not alter large arteriole constriction during LOS. We conclude that small arteriole vasodilation in skeletal muscle is mediated at least in part by EDRF during bacteremia. Because EDRF cannot mediate large arteriole constriction and because HQ blunted large arteriole constriction during HOB, we now suspect that HQ also interferes at least in part with some large arteriole vasoconstrictor mechanism, possibly leukotrienes or an endothelium-derived constricting factor, which mediates large arteriole constriction during HOB. Our data also suggest that large arteriole constriction during LOS is partly mediated by factors that are unaffected by HQ. The endothelium appears to play an important role in the microcirculatory responses of skeletal muscle to live E. coli sepsis through more than one mechanism.

Acetylcholine↗
PubMed1992

Infections of Gyrodactylus bullatarudis and Gyrodactylus turnbulli on guppies (Poecilia reticulata) in Trinidad.

Gyrodactylus bullatarudis Turnbull, 1956, and Gyrodactylus turnbulli Harris, 1986, are recorded from guppies (Poecilia reticulata) from the northern mountains of Trinidad. Mixed infections of the 2 species were found at 9 localities. Gyrodactylus turnbulli had a predominantly posterior distribution on the fishes, whereas G. bullatarudis was more anteriorly distributed. This is the first record of these species from guppies collected from within their original range.

Animals↗
PubMed1992

Alteration of microvascular responses to serotonin in the diabetic rat.

This study examined the microvascular response to serotonin (5-hydroxytryptamine; 5-HT) in short-term streptozotocin-induced diabetic rats. 5-HT was applied topically to the neurovascularly intact and environmentally controlled cremaster muscle of the two-week diabetic rat. Intravital microscopy was used to measure the diameters of large arterioles (First-order; A1) and small arterioles (Third-order; A3), and the FITC-albumin leakage in small venules (Third-order; V3). The diabetic animals were divided into two groups based on the dilator capacity of the A3 arterioles: the Diabetic-Tone group had a dilator capacity of 98 +/- 14.5% compared to 11 +/- 4.1% for the Diabetic No-Tone animals. 5-HT caused significantly greater constriction of A1 arterioles in Diabetic-Tone animals (-40 +/- 6%) than in either the Control (-19 +/- 6%) or Diabetic No-Tone (-18 +/- 5%) animals. 5-HT dilated the A3 arterioles to a similar degree in both the Diabetic-Tone and Control groups, but the Diabetic No-Tone group did not dilate to 5-HT because the A3 arterioles in these animals possessed no basal tone. Control animals showed a large 5-HT concentration-dependent increase in leakage of albumin in V3 venules, but this response was inhibited in the Diabetic-Tone animals. The 5-HT-induced leakiness in the Diabetic No-Tone group was intermediate between the other two groups. These results show that large arteriole constriction and small venule permeability responses to 5-HT are altered early in the development of diabetes, and are different in those animals with and without basal arteriolar tone. These data suggest that streptozotocin-induced diabetes alters microvascular function in striated muscle by at least two different cellular mechanisms.

Animals↗
PubMed1992

Altered endothelial mechanisms blunt skeletal muscle microcirculatory responses to live E. coli sepsis in 1K1C hypertension.

While renovascular (1K1C) hypertension significantly attenuates small arteriole dilation to sepsis in skeletal muscle of rats, maximal dilation of these small arterioles is not altered in response to an endothelium-independent vasodilator (nitroprusside). This suggests that 1K1C hypertension modifies a receptor-level mechanism to reduce small arteriole vasodilation during sepsis. To test this hypothesis, we used hydroquinone (HQ) to block an endothelium-derived relaxing factor (EDRF) in skeletal muscle arterioles of sodium pentobarbital (45 mg/kg BW)-anesthetized 1K1C-renovascular hypertensive male Sprague-Dawley rats which were then made septic. We found that responses of large and small arterioles to sepsis were blunted in hypertensive rats and that these responses were unchanged during the presence of HQ. This suggests 1) that blockade of some vasodilator mechanisms does not unmask an enhanced vasoconstrictor influence during sepsis in 1K1C hypertension and 2) that EDRF mechanisms are blunted by 1K1C hypertension. To further test this second idea, we examined the responses of small arterioles to acetylcholine (ACH) in normotensive and renovascular (1K1C) hypertensive rats before and after EDRF blockade. Skeletal muscle small arterioles were essentially not reactive to ACH in the hypertensives and HQ did not change this response. However, some vasodilation in hypertensives occurred under very high ACH concentrations even during the presence of HQ. These data suggest that sepsis-induced small arteriole dilation in skeletal muscle is blunted because endothelium-mediated responses are impaired in renovascular hypertension. Nevertheless, EDRF-independent mechanisms appear to be left intact during this form of hypertension.

Acetylcholine↗
PubMed1979

Modification of alpha-adrenergic responses of small arteries by altered PCO2 and pH.

Closed-circuit television microscopy was used to measure in vivo small artery (75--140 microns) and vein (105--230 microns) diameters to determine if changes in tissue PCO2 and/or pH would alter the microvascular responses to norepinephrine. Sprague-Dawley rats were anesthetized with a combination of urethane (800 mg/kg) and alpha-chloralose (60 mg/kg). The cremaster muscle with intact circulation and innervation was suspended by sutures in a 60-ml bath which contained a modified Krebs solution (31 degrees C) that was buffered by Tris of bicarbonate. There were four groups of animals with different combinations of bath PCO2 and pH: (1) PCO2 less than 10 mm Hg and pH = 7.2, (2) PCO2 less than 10 mm Hg and pH = 6.9, (3) PCO2 = 60--70 mm Hg and pH = 7.2, and (4) PCO2 = 60--70 MM Hg and pH = 6.9. The maximal responses of the small artery and vein to norepinephrine were similar for the four groups. The artery sensitivity to norepinephrine was significantly lower for group 4 when compared to groups 1, 2 and 3, but there was no effect on small vein sensitivity. Thus, the combination of decreased pH and increased PCO2 reduces small artery sensitivity to norepinephrine in the cremaster muscle of the rat.

Animals↗
PubMed1979

Microvascular and clinical effects of altered peritoneal dialysis solutions.

Blood flow in the peritoneum is one of the more important factors governing the efficiency of peritoneal dialysis. Yet there have been no previous studies which relate alterations and control of the peritoneal microcirculation to dialysis efficiency. Thus, we used closed-circuit television microscopy to quantitative the in vivo response (changes in diameter) to dialysis solutions of the small arteries on the mesothelial surface of the rat cecum and arterioles of the rat cremaster muscle. These responses were correlated wiht solute clearances from multiple peritoneal dialysis performed in humans. In the cremaster, a transient constriction was followed by a prolonged dilation. pH adjustments of the dialysis solution from 5.6 to 7.4 had no effect on the microvascular response and no effect on solute clearances during human peritoneal dialysis. In the cecum, dialysis solution caused a prolonged dilation which reached a maximum in about 10 min. Since dilation appears to be an important determinant of solute clearances during human peritoneal dialysis, the effects of a vasodilator, sodium nitroprusside, were determined. Sodium nitroprusside decreased the time to maximal dilation, which correlated clinically with an increased solute clearance during exchanges with this drug. Since nitroprusside increased clearances of the larger molecular weight solutes proportionally more than the smaller molecular weight solutes did, we hypothesize that nitroprusside increases solute clearances by both a vasodilatory effect and by an effect on vascular membrane permeability and area for solute exchange.

Animals↗
PubMed1979

Microvascular responses to norepinephrine in renovascular and spontaneously hypertensive rats.

Closed-circuit television microscopy was used to quantitate the responses of in vivo small arteries (50-140 micrometer diam) and veins (95-265 micrometer) to topically applied norepinephrine in the cremaster muscle of four groups of urethan-chloralose anesthetized rats. The rat groups were: Sprague-Dawley control (SDC), Sprague-Dawley renovascular hypertensive (RVH), Wistar-Kyoto control (WKY), and spontaneous hypertensive (SHR). The cremaster muscle with intact circulation and innervation was suspended by sutures in a 60-ml bath of bicarbonate-buffered Krebs solution. The vascular responses to the addition of progressively higher concentrations of norepinephrine to the bath were quantitated to obtain concentration-response curves. We found that the RVH (vs. SDC) had a decreased small-artery control diameter and decreased sensitivity to norepinephrine, whereas the SHR (vs. WKY) had tachycardia and decreased small-vein control diameter. Thus, the microvascular characteristics of these two types of hypertension appear to be quite different.

Animals↗
PubMed1979

Peritoneal clearances with three types of commerically available peritoneal dialysis solutions. Effects of pH adjustment and intraperitoneal nitroprusside.

Peritoneal clearances were measured in multiple patients with different types of peritoneal dialysis solution to assess the effects of pH, choice of buffer anion (acetate versus lactate), and the effects of nitroprusside (a vasodilator) in combination with different buffer anions and varying pH. The studies show no differences in peritoneal clearances at very low solution pH (less than 6 as is commonly available) as compared to a pH nearer to 7 or above. There were no diffences between solutions with acetate as compared to those with acetate. Nitroprusside significantly increased clearances in all solutions to a similar extent.

Acetates↗
PubMed1979

Clinical studies with a nonvasoactive peritoneal dialysis solution.

Topical application of dialysis solution to the rat microcirculation causes a transient vasoconstriction for 2 to 3 min. We assessed the clinical importance of this vasoconstriction by developing a dialysis solution without vasoactive properties, as assessed in the microcirculatory laboratory. The solution was of similar composition to human extracellular fluid. We tested its effects on Cur, Ccr, Cin, and dialysate protein concentration. We found that compared to commercial solutions, the lower osmolality of the NVS resulted in loss of ultrafiltration and decreases in clearance of urea and creatinine. The clearance of inulin was unchanged, and dialysate protein increased, suggesting a major increase in diffusive transport of large solutes. Increased diffusive transport of large solutes with NVS suggests that initial vasoconstriction seen in the rat could be present and clinically important during peritoneal dialysis in humans.

Adolescent↗
PubMed1978

Survival and microvascular responses to hemorrhage with three anesthetic combinations.

The effects of different anesthetic combinations on the responses to hemorrhage were investigated while using a single fixed protocol. Small artery (x +/- SE = 112 +/- 3 micron)) and vein (172 +/- 5 micron) responses to hemorrhage were quantitated in the cremaster muscle of 38 Sprague-Dawley rats via closed-circuit television microscopy. Rats were anesthetized intraperitoneally with pentobarbital (50 mg/kg), urethan (800 mg/kg), and alpha-chloralose (60 mg/kg), or urethan (600 mg/kg) and alpha-chloralose (120 mg/kg). After a 15-min control period, arterial blood pressure was lowered to 30 mmHg and maintained at that level for 60 min via hemorrhage from the femoral artery. The hemorrhaged blood was then reinfused, and recovery was monitored for 30 min. Survival was monitored for 7 days. Rats with heavier body weights (greater than or equal to 160 g) had a significantly greater survival rate, 81%, than did the lighter weight rats (less than 160 g), with a 32% survival rate. There were, however, no statistical differences in survival or microvascular responses among rats anesthetized with the three combinations of anesthetics. The combined data for all rats were: survival, 53%; small artery constriction, 45 +/- 2%; and small vein constriction, 21 +/- 3%.

Animals↗
PubMed1976

Sensitivity of small subcutaneous vessels to altered respiratory gases and local pH.

Television microscopy was used to quantitate the responses of small arteries and veins, in the wings of unanesthetized bats, to alterations in the inspired concentrations of O2 and CO2. Mean arterial pressure, heart rate, and the diameters of small arteries (28-54 mum) and veins (50-128 mum) were measured during a 90-min protocol--30 min with an inspiratory gas mixture of 20% O2 and 80% N2 (control period); 30 min with a gas mixture containing 5% O2 (hypoxic period) or 12, 20, or 28% CO2 (hypercapnic period); and 30 min with the original control gas. The hypoxic responses were dilatation of arteries and no change in the veins in both innervated and surgically denervated wings. Hypercapnia resulted in artery dilatation in innervated wings. Hypercapnia resulted in artery dilatation in innervated wings and constriction in denervated wings. The veins constricted in both innervated and denervated wings during the hypercapnia period. In another series, topical application of Krebs solutions (pH ranging from 7.7 to 6.7) to exposed segments of small arteries and veins produced dilatation of both vessels with decreasing pH. Artery dilatation during hypoxia and vein constriction during hypercapnia involve non-neural mechanisms, while both a neural stimulus for dilatation and a non-neural stimulus for constriction are components in the response of innervated arteries to hypercapnia. The non-neural stimulus for artery and vein constriction during hypercapnia is not a local decrease in pH.

Animals↗
PubMed1976

Continuous measurement of vascular diameters via television microscopy.

In the past 10 years, microcirculation studies have emphasized quantitative measurements of microvascular diameters to characterize in vivo small vessel responses to experimental forcings such as hemorrhage, anesthesia, and hypoxia. We have developed an instrument to obtain continuous diameter measurements of a small artery and vein (40-200 mu) via closed-circuit television microscopy. The outputs are analog voltages proportional to the vessel diameters. Video processing is limited to two image areas termed "windows," which are defined by markers on the monitor and positioned over separate vertically aligned vessels. Each vessel, which appears darker than the surrounding tissue, is located by comparing the video signal to a reference voltage that adapts to changes in the relative contrast within the window. In the presence of a vessel, a ramp voltage is generated, the peak value of which is proportional to the vessel diameter. These peaks are averaged over the 15-video lines of the window and over several video frames to reduce noise sensitivity. In order to accommodate preparation movement such as skeletal muscle contraction, window position and width automatically adapt to changes in vessel position and width. Visual verification of system performance is provided by clamping the video signal to white on that portion of the image which the instrument identifies as vessel.

Arteries↗