Search PubMed⌕ Search

Biomedical subjects

I G Joshua

Publications and source records attributed to I G Joshua.

At least 55 records · Page 3Linked to original sources
PubMed1982

Microvascular response to blockade of prostaglandin synthesis in rat skeletal muscle.

The contribution of endogenous prostaglandins (PGs) to the control of arteriolar diameter in the microcirculation is incompletely defied and has only been studied in drug-anesthetized animals. To test the possibility that endogenous PGs are tonically released to exert a net dilator influence at certain levels in the microcirculation, television microscopy was used to quantitate the arteriolar responses in the rat cremaster muscle to local blockade of PG synthesis with indomethacin. Rats were decerebrated by a midcollicular transection and were allowed to recover from surgical anesthesia. The cremaster muscle with intact circulation and innervation was suspended by sutures in a temperature-controlled Krebs bath. Diameters, vasomotion frequency, and vasomotion amplitude of arterioles at several anatomic levels were measured before and after local inhibition of PG synthesis in the presence and absence of alpha-adrenergic receptor blockade. Inhibition of PG synthesis produced marked constriction (42-66% of control) at all arteriolar levels, with greater responses occurring in the smaller arterioles. PG synthesis blockade increased vasomotion frequency in arterioles that exhibited spontaneous vasomotion during control periods, and blockade induced vasomotion in vessels lacking spontaneous vasomotion. Pretreatment with phentolamine significantly attenuated the constriction and augmentation of vasomotion. These data indicate that dilator PGs participate in the moment-to-moment regulation of arteriolar tone and local blood flow in skeletal muscle. Further, their mechanism of action may involve alterations in neuronal norepinephrine release or alpha-receptor sensitivity.

Animals↗
PubMed1981

Hyperosmolality, acetate, and lactate: dilatory factors during peritoneal dialysis.

Factors that alter peritoneal blood flow may influence the clearance of solutes during peritoneal dialysis. Arteriolar vasodilation, for instance, could increase the delivery of solutes to the capillaries and venules leading to an increase in solute transport into the peritoneal cavity. This study was designed to identify the vasoactive effects of several major components of McGaw and Dianeal peritoneal dialysis solutions to understand how the composition of these solutions may alter in vivo blood flow in the peritoneum. Because the major differences between these solutions and Krebs solution are a high osmolality, a high dextrose concentrations, and an acetate or lactate buffer system, we investigated the effects of these components. Rats were anesthetized with the combination of urethane and chloralose. The cremaster muscles, with the nerve and blood supplies from the rat still intact, was placed in a specially designed tissue chamber that was filled with Krebs solutions. A port permitted microscopic observations of the blood vessels. In vivo television microscopy observations was used to quantitate changes in small arteriole diameters induced by changes in the composition of the solution bathing the cremaster or by the addition of nitroprusside. Hyperosmolality produced by the addition of dextrose, sucrose, or sodium chloride to the Krebs solution induced a submaximal dilation of the small arterioles of the cremaster. The rate of dilation differed depending on the substance used to increase osmolality. A normal osmolality acetate (74 mM) or lactate (45 mM) solution produced a slow, submaximal dilation of the cremaster arterioles. Hyperosmolar acetate (37 or 74 mM) or lactate (45 mM) solutions produced a rapid, maximal dilation of these vessels. Because the rate of dilation and maximal effect produced by the commercial dialysis solutions were similar to these same parameters produced by the high-osmolality acetate or lactate solutions, the dilatory effects of McGaw and Dianeal solutions appear to be due to the combinations of high osmolality and the buffer anion acetate or lactate.

Acetates↗
PubMed1981

Regulation of calcium appetite in broiler chickens.

The regulation of the appetite for calcium was studied in broiler chickens which had been trained to meet their calcium requirement by consuming a calcium supplement (10% Ca) provided separately from a calcium-deficient feed (0.12% Ca). Calcium supplement intake was reduced within 150 minutes after intravenous injection of 60 U/kg parathyroid hormone or continuous infusion of 0.077 mg/minute calcium into one common carotid artery. Supplement consumption was also depressed during the first 8 days of continuous infusion of 1 U/kg/hour parathyroid hormone; after 8 days the birds became refractory. Continuous infusion of 0.2 Medical Research Council (MRC) units/kg salmon calcitonin for 10 days or daily intramuscular injections of 1 mg/kg testosterone propionate and 2 mg/kg estradiol dipropionate for 12 days, either alone or in combination, had no effect on calcium appetite. It is concluded that the calcium appetite may be inhibited by increased concentrations of ionic calcium in blood and that the change in behavior is sufficiently rapid to play a role in the calcium homeostasis of birds.

Animals↗
PubMed1981

Decreased vascular sensitivity to norepinephrine following exercise training.

Twenty Sprague-Dawley rats (230 +/- 9 g; mean +/- SE) were exercised daily for 6 wk by swimming 1 h/day with weights (5% of body wt) attached to their tails. Nineteen additional rats (237 +/- 8 g) remained sedentary in their cages. All animals were anesthetized with urethan (800 mg/kg) and alpha-chloralose (60 mg/kg). In the first series of experiments, increasing doses of norepinephrine were injected into the jugular vein and the responses in mean arterial blood pressure was recorded from a cannulated femoral artery. Exercise training had no effect on the maximal increase in blood pressure, but significantly decreased blood pressure sensitivity to norepinephrine, expressed as a pD2 value (=-log ED 50), from 5.64 +/- 0.07 to 5.20 +/- 0.06. In the second series, the cremaster muscle with intact circulation and innervation was suspended in a tissue bath and norepinephrine in increasing concentrations was added to the cremaster bath. The responses of the main arteriole (approximately 110 micron) and venule (approximately 170 micron) were recorded by television microscopy. Exercise training had no effect on vessel diameters of resting muscle or on the maximal vessel constrictions obtained in response to high concentrations of norepinephrine. Arteriole sensitivity to norepinephrine was significantly decreased (pD2 of 6.69 +/- 0.24 vs. 5.96 +/- 0.18) and there was some tendency for reduced venule sensitivity. These data suggest that exercise training in rats produces a decrease in alpha- or an increase in beta-adrenergic receptor sensitivity.

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

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↗
PubMedDate not supplied

In vivo arteriolar dilation in response to parathyroid hormone fragments.

The in vivo responsiveness of small arterioles to the topical administration of two parathyroid hormone fragments was investigated using television microscopy. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital (50 mg/kg) and second- and third-order arterioles in the cremaster muscle were exposed to increasing concentrations (2 X 10(-5) to 6 X 10(-4) mg/ml) of either hPTH (1-34) or bPTH-(3-34). Second- and third-order arterioles within the cremaster dilated (183% and 281% of control, respectively) following exposure to PTH-(1-34) in bath concentration of 10(-4) mg/ml and above. The dilation associated with PTH administration was abolished in second-order and greatly attenuated for third-order arterioles when the first two amino acid residues of the PTH molecule were removed (PTH (3-34) fragment). Inhibition of endogenous prostaglandins synthesis with mefenamic acid did not attenuate the vasodilator response to PTH. However, exposure to the muscarinic blocking agent atropine (10(-7) g/ml) totally inhibited the dilator response to PTH-(1-34). These data suggest that PTH induces arteriolar dilation by stimulation of muscarinic receptors in the vasculature possibly by causing the release of endogenous acetylcholine.

Acetylcholine↗
PubMedDate not supplied

Neuropeptide Y-induced constriction in small resistance vessels of skeletal muscle.

The in vivo responsiveness of small arterioles and venules in the rat cremaster muscle to topical administration of neuropeptide Y was assessed using closed-circuit television microscopy. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital (50 mg/kg) and the cremaster muscle was exposed to increasing bath concentrations of neuropeptide Y (10(-10)-10(-7) M). Neuropeptide Y produced dose-dependent constrictions in first (90 +/- 8 microns), second (50 +/- 6 microns) and third (21 +/- 4 microns) order arterioles. Arteriolar reactivity to the peptide was inversely related to vessel diameters. Venules were relatively unresponsive to neuropeptide Y. Exposure to the alpha-adrenergic receptor antagonist, phentolamine (10(-6) M), failed to modify the arteriolar constrictor responses to neuropeptide Y, while pretreatment with the sympathetic neuronal blocking agent, guanethidine (10(-5) M), produced a small, but significant, reduction in sensitivity. These data suggest that neuropeptide Y causes constriction of arterioles of skeletal muscle, primarily by acting directly on vascular smooth muscle to induce contraction, and not via release of endogenous norepinephrine.

Animals↗
PubMedDate not supplied

Met-enkephalin-induced vasoconstriction in the microcirculation of rat striated muscle.

Sprague-Dawley rats were anesthetized with pentobarbital (50 mg/kg) and the arterioles of the cremaster muscle were observed using television microscopy. Methionine (Met)-enkephalin was added to give bath concentrations of 10(-11) to 10(-7) M. Met-enkephalin caused a decrease in the diameter of first-order (127 +/- 7 microns), second-order (57 +/- 7 microns), and third-order (18 +/- 2 microns) arterioles, with the third-order arterioles showing the greatest reactivity. The effects of Met-enkephalin were attenuated by the opiate antagonist, naloxone, by the alpha-adrenergic receptor antagonists, phentolamine and prazosin, and by chemical sympathectomy with 6-hydroxydopamine. These results suggest that Met-enkephalin causes vasoconstriction in the striated muscle microcirculation by stimulating norepinephrine release from local nerve terminals.

Animals↗
PubMedDate not supplied

Comparison of early microcirculatory and aortic changes in hypercholesterolemic rats.

The microcirculatory changes caused by hypercholesterolemia were studied in the rat cremaster muscle model by intravital microscopy and were compared with aortic ring segments from the same animals. Male Sprague-Dawley rats were fed either a normal chow diet or a chow diet supplemented with 1% cholesterol and 0.5% cholic acid for 3 or 5 weeks before experimentation. Three weeks of hypercholesterolemia produced a significantly decreased vasodilator response to serotonin in the arterioles. This response was also seen after 5 weeks on the hypercholesterolemia diet. Three weeks of hypercholesterolemia produced a significantly increased macromolecular leakage from postcapillary venules in response to serotonin. However, after 5 weeks of hypercholesterolemia, the serotonin-induced leakage was less than in control animals. Hypercholesterolemia for 3 weeks decreased the arteriolar dilation evoked by acetylcholine but did not change the arteriolar response to sodium nitroprusside. Contraction of the aortic rings induced by serotonin and aortic ring relaxation induced by sodium nitroprusside were not different between 3-week-control and 3-week-hypercholesterolemic animals. However, 3 weeks of hypercholesterolemia attenuated the aortic ring relaxation evoked by acetylcholine. These results suggest that hypercholesterolemia causes an early depression of endothelium-derived relaxing factor (EDRF)-mediated receptor responses in both microvessels and the aorta, whereas non-EDRF-mediated receptor responses are altered in the microcirculation but not in the aorta.

Acetylcholine↗
PubMedDate not supplied

Distributions of microvascular pressure in skeletal muscle of one-kidney, one clip, two-kidney, one clip, and deoxycorticosterone-salt hypertensive rats.

Studies were performed on the cremaster skeletal muscle in rats to investigate the microvascular changes that are associated with established one-kidney, one clip (1K1C) and two-kidney, one clip (2K1C) Goldblatt hypertension and with deoxycorticosterone (DOC)-salt hypertension. Rats were anesthetized with urethane and chloralose; and cremaster muscles with intact circulation and innervation were suspended in a controlled Krebs bath. Microvascular pressures and vessel diameters were measured at three consecutive arteriolar (A) and venular (V) branch levels. Arteriolar diameters (means +/- SEM) in normotensive (NT) rats were 119 +/- 7, 86 +/- 5, and 31 +/- 3 micron respectively for 1A, 2A, and 3A arterioles; and venule diameters were 218 +/- 12, 141 +/- 15, and 53 +/- 7 micron respectively for 1V, 2V, and 3V venules. As compared to NT rats, there was a selective decrease in lumen size (percent reduction from control) for 1A and 2A (23% to 38%) in 1K1C and 2K1C rats and for 1A, 2A, and 3A (42% to 44%) in DOC rats. Venule diameters were not significantly different between normotensive and hypertensive animals at any branch level. Femoral artery pressures were significantly elevated (greater than or equal to 43%) in all three forms of hypertension; however, this increase in pressure was not proportionally transmitted throughout the microcirculation. This was evidenced by normal pressure in 3A arterioles and in all venules for 1K1C and 2K1C rats and by normal pressures in 3V and larger venules for DOC rats. Our findings indicate that elevated arterial pressure in chronic renal hypertension is not transmitted uniformly across all microvascular segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗