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Biomedical subjects

J S Morton

Publications and source records attributed to J S Morton.

7 recordsLinked to original sources
PubMed2007

Endothelium dependent relaxation in rabbit genital resistance arteries is predominantly mediated by endothelial-derived hyperpolarizing factor in females and nitric oxide in males.

PURPOSE: In nongenital arteries a sex difference has been postulated in the dominant endothelium-derived relaxant factor(s), eg nitric oxide, prostacyclin or endothelial-derived hyperpolarizing factor. Knowledge of endothelium-derived relaxant factor mechanisms in genital tissues could influence the development of novel treatments for sexual dysfunction. We compared nitric oxide and endothelial-derived hyperpolarizing factor contributions to acetylcholine induced relaxation in the genital arteries of the 2 sexes. MATERIALS AND METHODS: Male dorsal and cavernous penile arteries, and female extravaginal and intravaginal arteries from New Zealand White rabbits were studied. Acetylcholine concentration-vasodilator response curves were constructed in the presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester, K(+) channel blockers (apamin and charybdotoxin) or a combination. Indomethacin was present throughout to exclude prostacyclins. RESULTS: Extravaginal artery relaxation was predominantly endothelial-derived hyperpolarizing factor induced. Apamin plus charybdotoxin decreased maximal relaxations from a mean +/- SEM of 77% +/- 4% to 23% +/- 3% in 6 preparations (p <0.01). However, nitric oxide and endothelial-derived hyperpolarizing factor contributed to overall function. Dorsal artery relaxation was largely nitric oxide induced. Nomega-nitro-L-arginine methyl ester decreased maximal relaxations from 90% +/- 3% to 41% +/- 9% (p <0.001) with no endothelial-derived hyperpolarizing factor involvement (p >0.05). In cavernous and intravaginal arteries nitric oxide and endothelial-derived hyperpolarizing factor contributed to acetylcholine induced relaxation, while nitric oxide predominated. Blocking nitric oxide synthase or K(+) channels indicated that myogenic tone and constitutive activity of endothelium-derived relaxant factors were present. Vasodilator nerve mediated responses were influenced by each with the former more effective. CONCLUSIONS: Vaginal inflow arteries showed a dominance of endothelial-derived hyperpolarizing factor, contrasting with nitric oxide in penile arteries. Penile arteries followed the trend that endothelial-derived hyperpolarizing factor involvement increased with decreasing vessel caliber, while the reverse was demonstrated in female arteries.

Animals↗
PubMed2006

Alpha(1A)-adrenoceptors mediate contractions to phenylephrine in rabbit penile arteries.

BACKGROUND AND PURPOSE: Maintained penile erection depends on the absence of alpha-adrenoceptor (alpha-AR) activation and so can be facilitated by alpha-blockers. This study seeks the alpha(1)-AR subtypes involved in order to inform the pro-erectile consequences of subtype selective blockade. EXPERIMENTAL APPROACH: Wire myography was used with dorsal (nutritional supply) and cavernous (erectile inflow) penile arteries; standard alpha-AR-selective agonists and antagonists were employed to classify responses. KEY RESULTS: In both penile arteries noradrenaline (NA) and phenylephrine (PE, alpha(1)-AR agonist) caused concentration-dependent contractions. Sensitivity to NA was increased by NA uptake blockers, cocaine (3 microM) and corticosterone (30 microM). PE responses were antagonised by phentolamine (non-selective alpha-AR: dorsal pK(B) 8.00, cavernous 8.33), prazosin (non-subtype-selective alpha(1)-AR: dorsal 8.60, cavernous 8.41) and RS100329 (alpha(1A)-AR selective: dorsal 9.03, cavernous 8.80) but not by BMY7378 (alpha(1D)-AR selective: no effect at 1-100 nM) or Rec15/2615 (alpha(1B)-AR selective: no effect at 1-100 nM). Schild analysis was straightforward in cavernous artery, indicating that PE activates only alpha(1A)-AR. In dorsal artery Schild slopes were low, though alpha(1A)-AR was still indicated. Analysis using UK 14,304 and rauwolscine indicated an alpha(2)-AR component in dorsal artery that may account for low slopes to alpha(1)-AR antagonists. CONCLUSIONS AND IMPLICATIONS: Penile arteries have a predominant, functional alpha(1A)-AR population with little evidence of other alpha(1)-AR subtypes. Dorsal arteries (nutritional supply) also have alpha(2)-ARs. Thus, alpha-AR blockers with affinity for alpha(1A)-AR or alpha(2)-AR would potentially have pro-erectile properties; the combination of these perhaps being most effective. This should inform the design of drugs to assist/avoid penile erection.

Adrenergic alpha-Agonists↗
PubMed2005

Relationship between visual field loss and contrast threshold elevation in glaucoma.

BACKGROUND: There is a considerable body of literature which indicates that contrast thresholds for the detection of sinusoidal grating patterns are abnormally high in glaucoma, though just how these elevations are related to the location of visual field loss remains unknown. Our aim, therefore, has been to determine the relationship between contrast threshold elevation and visual field loss in corresponding regions of the peripheral visual field in glaucoma patients. METHODS: Contrast thresholds were measured in arcuate regions of the superior, inferior, nasal and temporal visual field in response to laser interference fringes presented in the Maxwellian view. The display consisted of vertical green stationary laser interference fringes of spatial frequency 1.0 c deg(-1) which appeared in a rotatable viewing area in the form of a truncated quadrant extending from 10 to 20 degrees from fixation which was marked with a central fixation light. Results were obtained from 36 normal control subjects in order to provide a normal reference for 21 glaucoma patients and 5 OHT (ocular hypertensive) patients for whom full clinical data, including Friedmann visual fields, had been obtained. RESULTS: Abnormally high contrast thresholds were identified in 20 out of 21 glaucoma patients and in 2 out of 5 OHT patients when compared with the 95% upper prediction limit for normal values from one eye of the 36 normal age-matched control subjects. Additionally, inter-ocular differences in contrast threshold were also abnormally high in 18 out of 20 glaucoma patients who had vision in both eyes compared with the 95% upper prediction limit. Correspondence between abnormally high contrast thresholds and visual field loss in the truncated quadrants was significant in 5 patients, borderline in 4 patients and absent in 9 patients. CONCLUSION: While the glaucoma patients tested in our study invariably had abnormally high contrast thresholds in one or more of the truncated quadrants in at least one eye, reasonable correspondence with the location of the visual field loss only occurred in half the patients studied. Hence, while contrast threshold elevations are indicative of glaucomatous damage to vision, they are providing a different assessment of visual function from conventional visual field tests.

Adult↗
PubMed2004

Absorption of the cholic acid-conjugated peptide hormone cholylsecretin from the rat ileum in vivo.

AIMS: Previously, we demonstrated that gastrin peptides as long as 34 amino acids were absorbed from the ileum of rat after conjugation to the C24 position of cholic acid and that these peptides retained full biological activity. As absorption was specific to the ileum, it was inferred that the conjugated hormone was taken up by the bile salt transporters. We have now extended these experiments to a member of a different family of hormones, viz. secretin, a 27-amino acid hormone that stimulates serous secretions from the exocrine pancreas. METHODS: After conjugation to cholic acid, the degree of cholylsecretin absorption from the ileum of anaesthetized rats was assessed from the increase in pancreatic secretions. RESULTS: A complication to the study was that intra-ileal infusion of native secretin caused a transient increase in the levels of pancreatic secretions. This was in contrast to the effects of intra-ileal infusion of cholylsecretin which did not cause this transient increase but, instead, gave rise to a delayed increase in pancreatic secretions which was sustained over several hours during which cholylsecretin was detected in plasma in high concentration by mass spectrometry. The pancreatic response to cholylsecretin was abolished by co-infusion of 50 mm taurocholate, employed to compete with the bile salt transporters, although a transient increase in pancreatic secretions similar to that caused by secretin was now generated. This was shown to arise from an action of taurocholate per se causing the release of endogenous secretin which is present in rat ileum. CONCLUSIONS: We, therefore, concluded that cholylsecretin had been absorbed from the rat ileum by uptake by bile salt transporters.

Absorption↗
PubMed1983

Iodine-129 in mule deer thyroids in the Rocky Mountain West.

Thyroids from mule deer (Odocoileus hemionus) were collected in New Mexico, Colorado, Wyoming and Idaho and 129I/127I atom ratios were determined. Iodine-129/127 atom ratios were significantly (P less than 0.005) different among states. Ratios in Wyoming and Idaho control thyroids were significantly (P less than 0.05) larger than ratios in New Mexico and Colorado. Fallout from past atmospheric nuclear tests at the Nevada Test Site is suggested as a possible explanation for the differences in ratios. Average 129I/127I ratios in thyroids of other large mammals collected 54 km west and 116 km northeast of the Idaho National Engineering Laboratory (INEL) in south eastern Idaho were up to 15 times those found in control thyroid samples from Idaho. Atmospheric effluents from the Idaho Chemical Processing Plant located on the INEL were likely responsible for the increased ratios in animals collected in the INEL vicinity. Although of no health consequence to the animals, 129I in deer thyroids may be a sensitive indicator of contaminants from nuclear fuel reprocessing plants and atmospheric nuclear tests or accidents.

Animals↗