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Biomedical subjects

P A Longhurst

Publications and source records attributed to P A Longhurst.

At least 91 records · Page 5Linked to original sources
PubMed1990

Short term functional effects of bladder outlet obstruction in the cat.

Experimental bladder outlet obstruction in cats was produced by surgical placement of a silastic cuff around the urethra. Two sizes of cuff were used to produce either moderate or severe obstruction. The following is a summary of the short-term effects on bladder function. Obstruction induced a significant increase in the in vivo voiding pressure, in proportion to severity of the obstruction. There were no significant differences between control and obstructed cats in bladder mass, response of the isolated whole bladder to field stimulation or bethanechol, response of isolated bladder strips to field stimulation, bethanechol and ATP, or muscarinic receptor density in the bladder body. Although there were no differences in bladder mass between control and obstructed bladders, the hydroxyproline concentration of the severely obstructed bladders was significantly reduced. Creatine phosphate concentration was also significantly reduced in obstructed bladders. Although all whole cat bladder preparations displayed spontaneous contractile activity during in vitro cystometry, the obstructed bladders had a greater amplitude and frequency of spontaneous contractions with a lower volume threshold. In addition, the obstructed bladders had a greater tetrodotoxin-resistant contractile response to field stimulation. These results suggest that the obstructed cat bladder can compensate for increased outlet resistance without induction of bladder hypertrophy or significant functional changes, as seen in both rat and rabbit.

Adenosine Triphosphate↗
PubMed1990

Length-tension relationship of urinary bladder strips from streptozotocin-diabetic rats.

Streptozotocin-induced diabetes mellitus or the consumption of 5% sucrose in place of drinking water cause an increase in rat urinary bladder capacity and mass. Length-tension curves were generated using bladder body strips isolated from control, diabetic, or sucrose-drinking rats to determine whether the length-tension relationship was altered by the bladder hypertrophy associated with diabetic and nondiabetic diuresis. In addition, we compared the data using three different methods of expression: (1) absolute grams tension developed; (2) grams tension/100 mg tissue, and (3) grams tension/mm2. The cross-sectional area of strips from diabetic rats was increased compared to the other two groups. The length-passive tension curves for all three groups increased with increasing tissue length to a plateau. No optimal resting length for generation of active tension was found. Strips from diabetic and sucrose-drinking rats reached the plateau at a slightly larger passive tension than did strips from control rats. In addition, strips from diabetic and sucrose-drinking rats generally developed a greater active tension than did strips from control rats depending on the method of data presentation used. The data suggest that the complex nonlinear arrangement of smooth muscle fibers in the bladder wall results in the unusual length-tension curves generated by urinary bladder strips (as compared to skeletal or vascular smooth muscle). This relationship would be of benefit in the urinary bladders of early-stage diabetic patients before neuropathy development, where the stretching of the bladder wall would allow accommodation without any compromise of bladder function. The data indicate that comparisons of bladder strip function from control and diabetic rats should be done at passive tensions of greater than or equal to 2 g to ensure that maximal active tension is generated.

Animals↗
PubMed1989

Effects of castration and diabetes mellitus on cholinergic responsiveness and muscarinic receptors in the rat vas deferens.

Studies were carried out to compare the effects of diabetes mellitus and castration on the muscarinic responsiveness of rat vasa deferentia. One and two months after castration or after streptozotocin-induced diabetes, there were significant decreases in serum testosterone levels, accompanied by significant decreases in vas deferens weights, protein contents, and protein concentrations. However, contractile responses of vasa deferentia from streptozotocin-diabetic or castrated rats to carbachol were significantly increased compared to controls. These changes were accompanied by increases in Kd and decreases in Bmax (pm/tissue) for 3H-quinuclidinyl benzilate (QNB) binding. Contractile responses and QNB binding were also studied in the spontaneously diabetic BB/W or rat, a less severely diabetic model than the streptozotocin-diabetic rat. Ninety days after the onset of diabetes in the BB rat, there was an increase in the contractile response to carbachol. There were qualitatively similar but smaller changes in vas deferens weights, protein contents, protein concentrations, and QNB binding than in the streptozotocin-diabetic rats. The data show that diabetes and castration increased the contractile responses of vasa deferentia despite decreases in protein content and in the number of muscarinic receptors. The results suggest that muscarinic receptor-effector coupling is more efficient in vasa deferentia from castrated or diabetic rats, resulting in a greater contractile response to cholinergic agonists.

Animals↗
PubMed1989

Comparison of the effects of castration and streptozotocin-induced diabetes mellitus on contractile responses of the rat vas deferens.

Contractile responses of androgen-sensitive smooth muscles such as the vas deferens and seminal vesicles are highly dependent upon the endocrine status of the animal. Although diabetes mellitus produces disturbances in reproductive function, including decreased serum androgen levels, the effects of diabetes on the contractile function of androgen-dependent urogenital smooth muscles have not been conclusively established. The present study compared the effects of streptozotocin-induced diabetes with those of castration on the contractile responses of rat vasa deferentia. Diabetes and castration produced significant decreases in serum testosterone levels, accompanied by significant decreases in vas deferens weights. Contractile responses of vasa deferentia from diabetic rats to carbachol, ATP, and phenylephrine were significantly increased, and responses to nerve stimulation were decreased. Similar results were obtained with vasa deferentia from castrated rats. Castration produced significant increases in contractile responses of vasa deferentia to carbachol and phenylephrine and decreased responses to nerve stimulation. The data suggest that both castration and diabetes produce a denervation-like supersensitivity which is specific for receptor-mediated processes.

Adenosine Triphosphate↗
PubMed1989

Effects of muscarinic stimulation on intracellular calcium in the rabbit bladder: comparison with metabolic response.

Urinary bladder emptying is mediated primarily by a co-ordinated contraction of the bladder body in response to parasympathetic stimulation and muscarinic receptor activation. In a previous study using surface spectrophotometry to monitor the nicotinamide adenine dinucleotide (oxidized form)/nicotinamide adenine dinucleotide (reduced form) (NADH/NAD) ratio, we demonstrated that muscarinic stimulation results in a rapid decrease in this ratio which precedes the contractile response, and that the ED50 for the NADH response is significantly lower than the ED50 for contraction. The current study was designed to correlate changes in intracellular free calcium using FURA-2 fluorescence with both the contractile and metabolic response to muscarinic stimulation. Isolated strips of urinary bladder body were monitored in vitro for changes in intracellular free calcium, NADH/NAD ratio, and contraction. Intracellular free calcium was monitored by preincubation with FURA-2 AM and continuously measuring the fluorescence with an MB2 surface spectrofluorometer using excitation wavelengths of 340 and 380 nm, and an emission wavelength of 510 nm. The NADH/NAD ratio was monitored with the MB2 surface spectrophotometer using an excitation wavelength of 366 nm and an emission wavelength of 450 nm. Contraction was monitored using an isometric force transducer connected to a Grass model D polygraph. The results can be summarized as follows: (1) Bethanechol stimulates a sharp decrease in the NADH/NAD ratio, a rapid increase in intracellular free calcium, and a slower increase in contractile force. (2) The ED50 for NADH fluorescence was significantly less than the ED50 for either contraction or calcium fluorescence which were equal to each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Changes in adrenocortical monooxygenase activities in alloxan-diabetic rabbits.

Studies were carried out to determine if diabetes mellitus influenced the activities of adrenal steroidogenic enzymes. Adult male rabbits were made diabetic by an i.v. infusion of alloxan (100 mg/kg) and were killed 1 or 2 months later. Mitochondrial cytochrome P-450 concentrations were not affected by diabetes but steroid 11 beta-hydroxylase activity was greater in the diabetics than in controls after both 1 and 2 months. The type I spectral change produced by 11-deoxycorticosterone, the substrate for 11 beta-hydroxylation, was also greater in mitochondria from diabetics. By contrast, mitochondrial cholesterol side-chain cleavage activity was similar in controls and diabetics. Microsomal cytochrome P-450 concentrations were unaffected by diabetes but 21-hydroxylase activity was significantly lower in adrenal microsomes from diabetics than from controls. The results indicate that alloxan-induced diabetes alters adrenocortical steroid metabolism which may contribute to changes in the pattern of steroid secretion noted by other investigators.

Adrenal Cortex↗
PubMed1988

Sensitivity of caudal arteries and the mesenteric vascular bed to norepinephrine in DOCA-salt hypertension.

This study was undertaken to determine what factors might contribute to arterial supersensitivity to norepinephrine associated with deoxycorticosterone acetate (DOCA)-salt hypertension in the rat. Experimental groups of male rats were uninephrectomized and 1 week later began receiving twice weekly injections of DOCA (20 mg/kg s.c. in sesame oil) plus 1% NaCl and 0.2% KCl in their drinking water. For each experimental group, a group of age-matched male rats underwent a sham operation and received injections of sesame oil and the NaCl-KCl drinking water. Perfused caudal arteries from 3-week-hypertensive rats were supersensitive to intraluminal and extraluminal norepinephrine administration. However, this difference in sensitivity between hypertensive and control caudal arteries was demonstrable at low rates of perfusion, 0.5 to 1.0 ml/min, but not at rates of 2.0 to 2.6 ml/min. The supersensitivity was not due to differences in neuronal uptake or to inhibition of extraneuronal uptake by DOCA. The perfused mesenteric vascular bed from 3- or 6-week-hypertensive rats was also supersensitive to intraluminal norepinephrine. However, the demonstration of supersensitivity in the mesenteric vasculature was independent of perfusion rate (2.3-6.8 ml/min) and perfusion pressure in the range of 30 to 60 mm Hg. There was little or no supersensitivity to transmural nerve stimulation in either the caudal artery or the mesenteric vasculature, a finding consistent with the observed decrease in endogenous norepinephrine content. Microelectrodes were used to determine resting membrane potential in the smooth muscle cells. No differences in resting membrane potential were detected between caudal or mesenteric arteries from hypertensive compared with control rats 2, 3, or 6 weeks after initiation of the DOCA-salt regimen. It is concluded that 1) the perfusion rate is a critical factor in designing experiments to test the sensitivity of caudal arteries to drugs, 2) the perfused mesenteric vascular bed is a useful preparation for studying sensitivity of blood vessels in hypertension, 3) the supersensitivity of blood vessels in the DOCA-salt model may be of greater importance relative to circulating catecholamines than to sympathetic innervation, and 4) the supersensitivity of blood vessels to norepinephrine in the DOCA-salt model is not due to changes in neuronal uptake, extraneuronal uptake, or membrane potential of the vascular smooth muscle cells.

Animals↗
PubMed1987

A contrasting effect of the diabetic state upon the contractile responses of aortic preparations from the rat and rabbit.

Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (65 mg kg-1). Rabbits were rendered diabetic by injecting alloxan (100 mg kg-1) into the lateral ear vein. Diabetes was confirmed by a significant elevation of serum glucose in both species 8 weeks after injection. The maximum contraction to noradrenaline (NA), 5-hydroxytryptamine (5-HT) and KCl was markedly diminished in thoracic aortic rings (AR) from diabetic rats with no change in the EC50 of the agonists. There were no differences in the contractile properties of AR from diabetic rabbits to NA, 5-HT or KCl. Diabetes did not alter the responsiveness of AR from the rat to angiotensin II (AII). However, AR from diabetic rabbits displayed a decreased maximal contraction and an increased EC50 to AII. The magnitude of the acetylcholine-induced relaxation to precontracted AR was not different between diabetic and control rats and rabbits. The contractile responses of AR to NA, 5-HT and KCl were depressed in diabetic rats, regardless of the control tissue to which they were compared. The decrease in maximal contraction to NA, 5-HT and KCl seen in diabetic animals was prevented by insulin replacement. The results demonstrated that while both rats and rabbits exhibited a similar degree of hyperglycemia after treatment with a diabetogenic agent, aortic preparations from the rabbit are not affected in the same way as the aorta from the diabetic rat when exposed to NA, 5-HT and KCl. This feature may be related to the marked differences between the extent of sympathetic innervation of the aorta in the rabbit and rat. Furthermore, the decrease in maximal contraction in rat aorta was non-specific with respect to agonists since it could also be demonstrated with KCl. Therefore, it follows that the diabetic state may affect processes responsible for contraction beyond the level of receptor activation.

Acetylcholine↗
PubMed1986

Perfusion of the intact and partially isolated rat mesenteric vascular bed: application to vessels from hypertensive and normotensive rats.

In the present study, we utilized 2 perfused mesenteric vascular bed preparations in an examination of the responses of mesenteric vessels from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. One preparation involved perfusion of the mesenteric vascular bed dissected free from the intestine. The second preparation was essentially similar, with the exception that the intestine and the small arterioles feeding the jejunum were intact. The results suggested that the small vessels offer a significant contribution to the mechanical resistance to perfusion in the mesenteric vasculature and are important in the neurogenic responses of this preparation. In contrast, the arterioles in the arcade supplying the jejunum play only a minor role in the responses of the mesenteric vascular bed to intraluminally injected vasoactive substances. It was found that mesenteric preparations from SHR rats responded more forcefully to intraluminally administered norepinephrine and potassium, regardless of whether the intestine was absent or present. Similarly, the responses of mesenteric preparations to electrical nerve stimulation were greater in preparations from SHR rats, particularly when the intestine was present. It is concluded that the perfused mesenteric vasculature from SHR rats is more responsive to vasoactive substances and nerve stimulation and that this feature is not exclusively dependent upon a contribution to contraction by the arterioles supplying the jejunum.

Animals↗
PubMed1986

Abnormalities of rat bladder contractility in streptozotocin-induced diabetes mellitus.

Diabetic cystopathy is a common complication of diabetes mellitus, but little is known of the mechanisms responsible for the bladder dysfunction. Therefore, the effect of streptozotocin-induced diabetes on urinary bladder function was investigated. Bladders from 2-month diabetic rats were significantly larger than those from age-matched controls. Protein concentrations in bladder body and base were similar in diabetic and control rats. However, due to the greater bladder body weight in diabetic animals, total protein content of bladder bodies from diabetic rats was significantly greater than those from controls. Contractile responses of strips obtained from bladder body and base to stimulatory agents and nerve stimulation were altered by diabetes. In bladder bodies from diabetic rats, the maximal contractile responses to nerve stimulation, acetylcholine and KCl were reduced compared to controls. In addition there was a decreased sensitivity to acetylcholine and KCl in the diabetics. In contrast, with strips from bladder base there was a decrease in sensitivity to nerve stimulation in the diabetic rats, but no change in sensitivity to norepinephrine, acetylcholine, ATP or KCl. The maximal contraction by bladder base in response to norepinephrine was decreased in diabetic rats, but there was no change in maximal contraction by bladder base in response to norepinephrine was decreased in diabetic rats, but there was no change in maximal response to nerve stimulation, acetylcholine, ATP or KCl. These results indicate that a relatively nonspecific decrease in the responsiveness of bladder body is caused by diabetes, but agonist-specific changes are produced in bladder base.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1985

Hormonal influence on the neurogenic response of the hamster vas deferens.

The effect of castration on in vitro contractility of smooth muscle of the vas deferens and body of the bladder has been studied in the hamster. Castration produced supersensitivity to in vitro electrical stimulation and norepinephrine in the vas deferens, but had no effect on the body of the bladder. Castration also increased the maximum contractile response of the vas deferens to electrical stimulation, norepinephrine, ATP, acetylcholine and histamine. The changes in contractility of smooth muscle of the vas deferens developed slowly and may be explained by specific effects upon adrenergic and purinergic neurotransmission and/or non-specific effects upon smooth muscle cell membranes.

Acetylcholine↗
PubMed1985

Surgical sympathectomy of the heart in rodents and its effect on sensitivity to agonists.

A new procedure for sympathetic denervation of the hearts of rats and guinea pigs is described. Bilateral removal of the inferior and medial cervical ganglia results in almost complete loss of catecholamines from atria and ventricles, disappearance of catecholamine-associated histofluorescence from the region of the sinoatrial node and marked depression of the chronotropic concentration-response curve for tyramine in right atria of both species. Seven days after bilateral sympathectomy, the chronotropic concentration-response curve for isoproterenol is shifted to the left by a factor of 3.3 in the rat and 1.7 in guinea-pig right atria. The chronotropic concentration-response curve for histamine was not shifted by sympathectomy in the guinea-pig right atrium. Inasmuch as the rat atrium does not respond to histamine, similar experiments could not be done in the rat. The inotropic concentration-response curve for isoproterenol in electrically driven left atria was not affected by 7 days of sympathectomy in either species. These results indicate that chronic surgical sympathectomy of the heart can be successfully accomplished in the rat and guinea pig. Such sympathectomy induces a postjunctional supersensitivity in guinea-pig right atria which is qualitatively and quantitatively similar to that described previously for chronic treatment with reserpine. Bilateral surgical sympathectomy provides a valuable tool for future investigations of the cellular basis of supersensitivity in the myocardium.

Animals↗
PubMed1985

Responses of the isolated perfused mesenteric vasculature from diabetic rats: the significance of appropriate control tissues.

The influence of streptozotocin-induced diabetes on the contractile responses of the rat isolated perfused mesenteric vascular bed was determined. Two control groups were used, age-matched, fed ad-libitum rats and age-matched, food-restricted rats which were weight-matched to the diabetic group. Two months after the induction of diabetes there was a nonspecific decrease in contractile responsiveness of the mesenteric vascular bed from the diabetic rats to nerve stimulation, and to intraluminal norepinephrine and KCI compared to the responses of the control groups. There was no difference in the responsiveness of the two control groups to these vasoconstrictor treatments. The diabetes-induced depression of responses could be due to changes in vascular smooth muscle function, with an additional contribution of an abnormality in sympathetic neuronal function.

Animals↗
PubMed1984

A study of the atropine-resistant component of the neurogenic response of the rabbit urinary bladder.

Rabbit bladder body was stimulated to contract by a number of agonists, of which bradykinin was the most potent, and ATP one of the least potent substances tested. The atropine-resistant component of the neurogenic response was unaffected by 2 X 10(-5) M chlorpheniramine or 10(-6) M methysergide, doses which suppressed responses to histamine or 5HT. Indomethacin 10(-5) M, or 10(-5) M capsaicin both reduced the atropine-resistant component. Following treatment with 10(-6) M atropine and 10(-5) M prazosin, 10(-4) M ANAPP3 produced a further suppression of the response, but did not antagonize the response to ATP. In the bladder body, the transmitter(s) responsible for the neurogenic response may be acetylcholine and prostaglandins and possibly ATP and substance P.

Animals↗
PubMed1983

Guinea-pig and rabbit papillary muscles differ in their response to histamine.

Guinea-pig and rabbit papillary muscles differ in their response to histamine. 1. Basal developed force (BDF) and maximal developed force (MDF) following isoproterenol and histamine were determined in rabbit and guinea-pig papillary muscles under a variety of experimental conditions. Hypothermia and an increase in the calcium concentration increased the BDF in both tissues. 2. In the guinea-pig MDF increased to a similar extent following both agonists. In the rabbit the MDF response to histamine was much less than the response to isoproterenol. 3. In the guinea-pig papillary muscle, stimulation of both beta- and H2-receptors produces an increase in cyclic AMP. The rabbit papillary muscle contains H1-receptors, stimulation of which has no effect on cyclic AMP. The reduced MDF effect of histamine compared to isoproterenol in the rabbit may be due to the differing biochemical events following beta- or H1-stimulation.

Animals↗
PubMed1982

Rabbit atrial histamine receptors and cyclic AMP.

The present study confirms the presence of H2 receptors in rabbit right and left atrium by measuring changes in cyclic AMP. Histamine produced significant increases in cyclic AMP in both atria although the increases were less in left atria. Since H2 receptors are always associated with the adenylate cyclase--cyclic AMP system, the data provide further support for the suggestion that H2 receptors exit in rabbit right and left atria.

Animals↗