Biomedical subjects

Caryl E Hill

Publications and source records attributed to Caryl E Hill.

6 recordsLinked to original sources

PubMed2003

Structure, function, and endothelium-derived hyperpolarizing factor in the caudal artery of the SHR and WKY rat.

OBJECTIVE: To quantify structural and functional characteristics of the caudal artery from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats with particular reference to endothelium-derived hyperpolarizing factor (EDHF). METHODS AND RESULTS: Ultrastructural studies showed that the number of myoendothelial gap junctions, smooth muscle cell (SMC) layers, and medial cross-sectional area were significantly greater in SHR than WKY. Intracellular dye labeling demonstrated hyperplasia of SMCs in SHR. Analysis of nerve-mediated excitatory junction potentials recorded in SMCs at the adventitial and luminal borders demonstrated decreased radial coupling of SMCs in SHR. In both SHR and WKY, in the presence of NG-nitro-L-arginine methyl ester and indomethacin, acetylcholine-elicited EDHF was abolished by charybdotoxin and apamin, while iberiotoxin had no effect, implicating the involvement of small and intermediate, but not large, calcium-activated potassium channels. EDHF was abolished by Gap-mimetic peptides, 18beta-glycyrrhetinic acid, and endothelial removal but not affected by the NO scavengers hydroxocobalamin and carboxy-PTIO. CONCLUSIONS: Significant differences in SMC morphology and homocellular and heterocellular coupling exist between the caudal artery of SHR and WKY rats. In the caudal artery of SHR, significantly greater heterocellular coupling compensates for other structural changes in the media to maintain a functional role for EDHF.

Acetylcholine↗

PubMed2002

Connexin37 is the major connexin expressed in the media of caudal artery.

OBJECTIVE: To determine the connexins (Cxs) involved in intercellular coupling within vascular muscle, the present study has quantified mRNA and protein expression for Cx37, Cx40, Cx43, and Cx45 in the caudal artery (CA) and thoracic aorta (ThA) of the rat. METHODS AND RESULTS: Real-time polymerase chain reaction and immunohistochemistry identified Cx37 as the most abundantly expressed Cx in the CA, with fine punctate staining observed in the media. Conversely, mRNA for Cx43 was 40-fold greater in the ThA than in the CA, with punctate staining in the endothelium and media of the ThA but confined to the endothelium in the CA. Western blotting confirmed the differences in the relative amounts of Cx43 between the 2 vessels. For both arteries, Cx45 was expressed to a lesser degree in the media but not in the endothelium, whereas Cx40 was found only in the endothelium. Cx37, Cx40, and Cx43 were expressed in the endothelium of both vessels, although the density of Cx40 plaques was significantly greater in the CA. CONCLUSIONS: The demonstration of Cx37 as the dominant Cx in the media of the CA highlights the potential heterogeneity in Cx involvement in vascular smooth muscle.

Animals↗

PubMed2002

Involvement of myoendothelial gap junctions in the actions of endothelium-derived hyperpolarizing factor.

The nature of the vasodilator endothelium-derived hyperpolarizing factor (EDHF) is controversial, putatively involving diffusible factors and/or electrotonic spread of hyperpolarization generated in the endothelium via myoendothelial gap junctions (MEGJs). In this study, we investigated the relationship between the existence of MEGJs, endothelial cell (EC) hyperpolarization, and EDHF-attributed smooth muscle cell (SMC) hyperpolarization in two different arteries: the rat mesenteric artery, where EDHF-mediated vasodilation is prominent, and the femoral artery, where there is no EDHF-dependent relaxation. In the rat mesenteric artery, stimulation of the endothelium with acetylcholine (ACh) evoked hyperpolarization of both ECs and SMCs, and characteristic pentalaminar MEGJs were found connecting the two cell layers. In contrast, in the femoral artery, ACh evoked hyperpolarization in only ECs but not in SMCs, and no MEGJs were present. Selective hyperpolarization of ECs or SMCs evoked hyperpolarization in the other cell type in the mesenteric artery but not in the femoral artery. Disruption of gap junctional coupling using the peptide Gap 27 markedly reduced the ACh-induced hyperpolarization in SMCs, but not in ECs, of the mesenteric artery. These results show that transfer of EC hyperpolarization or of a small molecule to SMCs through MEGJs is essential and sufficient to explain EDHF.

Acetylcholine↗

PubMed2002

Microcirculation down under.

The Seventh World Congress for Microcirculation, organized by the Australian and New Zealand Microcirculation Society, was held on 19-22 August 2001 in Sydney, New South Wales, Australia.

Australia↗

PubMed2002

Expression of mRNA and functional alpha(1)-adrenoceptors that suppress the GIRK conductance in adult rat locus coeruleus neurons.

1. Locus coeruleus neurons in adult rats express binding sites and mRNA for alpha(1)-adrenoceptors even though the depolarizing effect of alpha(1)-adrenoceptor agonists on neonatal neurons disappears during development. 2. In this study intracellular microelectrodes were used to record from locus coeruleus neurons in brain slices of adult rats and reverse transcription-polymerase chain reaction (RT - PCR) was used to investigate the mRNA expression of alpha(1)- and alpha(2)-adrenoceptors in juvenile and adult rats. 3. The alpha(1)-adrenoceptor agonist phenylephrine had no effect on the membrane conductance of locus coeruleus neurons (V(hold) -60 mV) but decreased the G protein coupled, inward rectifier potassium (GIRK) conductance induced by alpha(2)-adrenoceptor or mu-opioid agonists. The GIRK conductance induced by noradrenaline was increased in amplitude when alpha(1)-adrenoceptors were blocked with prazosin. 4. RT - PCR of total cellular RNA isolated from microdissected locus coeruleus tissue demonstrated strong mRNA expression of alpha(1a)-, alpha(1b)- and alpha(1d)-adrenoceptors in both juvenile and adult rats. However, only mRNA transcripts for the alpha(1b)-adrenoceptors were consistently detected in cytoplasmic samples taken from single locus coeruleus neurons of juvenile rats, suggesting that this subtype may be responsible for the physiological effects seen in juvenile rats. 5. Juvenile and adult locus coeruleus tissue expressed mRNA for the alpha(2a)- and alpha(2c)-adrenoceptors while the alpha(2b)-adrenoceptor was only weakly expressed in juveniles and was not detected in adults. 6. The results of this study show that alpha(1)-adrenoceptors expressed in adult locus coeruleus neurons function to suppress the GIRK conductance that is activated by mu-opioid and alpha(2)-adrenoceptors.

Action Potentials↗

PubMed2002

Decreased endothelial size and connexin expression in rat caudal arteries during hypertension.

OBJECTIVES: Hypertension is accompanied by endothelial dysfunction. The present study has investigated endothelial cell morphology and connexin expression in the caudal artery of the rat during the development of hypertension. METHODS: A significant increase in systolic blood pressure was detected from 9 weeks of age in spontaneously hypertensive male rats (SHR) compared to normotensive Wistar-Kyoto (WKY) rats, reaching a maximum by 11-12 weeks of age. Immunohistochemistry was used to quantify cell size and expression of connexins (Cxs) 37, 40 and 43 in the endothelium of prehypertensive (3-week-old) and hypertensive (12-week-old) rats. RESULTS: At 12 weeks, the size of endothelial cells and the expression of all three Cxs per endothelial cell were significantly less in SHR than WKY rats. At 3 weeks, there was no significant difference in cell size nor in the expression of Cxs 37 or 43; however, expression of Cx40 was significantly lower in SHR than in WKY rats. Between 3 and 12 weeks in WKY rats, there was no change in endothelial cell size, nor in the expression of Cxs 37, 40 and 43. In SHR, both cell size and Cx expression per endothelial cell were significantly decreased during the same developmental period, with a significant decrease in the density of Cx40 plaques. CONCLUSION: The development of hypertension in the SHR is accompanied by significant decreases in endothelial cell size and expression of Cx40, which may contribute to the endothelial dysfunction present in hypertension.

Age Factors↗