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Biomedical subjects

R H Cox

Publications and source records attributed to R H Cox.

At least 217 records · Page 12Linked to original sources
PubMedDate not supplied

The borderline hypertensive rat (BHR): a new model for the study of environmental factors in the development of hypertension.

While many studies have attempted to produce hypertension through the use of various environmental stressors, few have succeeded in producing chronic elevations in blood pressure beyond levels considered to be borderline hypertensive (140-160 mm Hg systolic). The problem with most studies stems from the use of genetically normotensive animals and the selection of stressors to which animals readily adapt. A new approach is suggested, which recognizes the role of genetics in human essential hypertension. Animals with one hypertensive parent do not develop spontaneous hypertension but show a more sensitive cardiovascular response to environmental stressors than animals with normotensive parents. Preliminary studies revealed that animals with a mixed genetic history of hypertension develop spontaneous borderline hypertension. When subjected to shock-shock conflict, these borderline hypertensive rats (BHR) developed permanent hypertension that failed to abate even after a ten-week, shock-free recovery period. The hypertension was accompanied by elevated heart weight to body weight ratios and by significant cardiac pathology. Subsequent work has demonstrated that these animals also become hypertensive when fed a high-sodium diet. Finally, in a series of exercise studies, we found that BHRs subjected to a shock stressor were protected against stress-induced hypertension if they exercised daily. The potential of this model for studies of the mechanisms by which environmental variables produce permanent hypertension is discussed.

Aging↗
PubMedDate not supplied

The isolation and identification of several trichothecene mycotoxins from Fusarium heterosporum.

An isolate of Fusarium heterosporum Nees ex Fr. that parasitizes the honeydew and immature sclerotia of Claviceps paspali was shown to be highly toxigenic to day-old chickens. The major toxicity of culture extracts of the fungus was due to the presence of several trichothecene mycotoxins. Six trichothecenes were isolated and chemically identified by spectroscopic methods as T-2 toxin (1), HT-2 toxin (2), T-2 tetraol (6), 3alpha,4beta,dihydroxy-15-acetoxy-8alpha-(3-hydroxy-3-methylbutyryloxy)-12,13-epoxytrichothec-9-ene (3), 3alpha,4beta,15-trihydroxy-8alpha-(3-hydroxy-3-methylbutyryloxy)-12,13-epoxytri chothec-9-ene (5), and 3alpha,4beta,8alpha-trihydroxy-15-acetoxy-12,13-epoxytrichothec-9-ene (4). The acute toxicities of the trichothecenes were compared to the effects of T-2 toxin in day-old chickens and on the back skins of rabbits. The comparative inhibitory effects of the trichothecene mycotoxins in the Triticum coleoptile bioassays were also determined.

Animals↗
PubMedDate not supplied

Voltage-gated sodium channels in human aortic smooth muscle cells.

Whole-cell, voltage clamp methods were used to study inward currents in human aortic smooth muscle cells in culture. Cells were plated on glass coverslips, cultured in supplemented M-199 media with 5% serum and studied as primary cells and at passages 2-5. Inward currents were measured with a pipette solution containing Cs+ and TEA+ to block K+ currents and with 2.5 mM [Ca2+]0 in the perfusate. Inward currents activated at about -50 mV, peaked at about -15 mV and reversed at about +30 mV. Values of peak inward current averaged 14. 7 +/- 3.3 pA/pF and cell capacitance averaged 124 +/- 10 pF (n = 35). These currents activated rapidly with a time-to-peak current of 2.4 +/- 0.3 ms at a test potential of -10 mV from a holding potential of -80 mV. The current also inactivated rapidly with a time course that could be described by two components with time constants of 1.8 +/- 0.2 and 17.8 +/- 3.5 ms at -10 mV. The currents decreased when extracellular Na+ was reduced and were completely inhibited by 50 nM tetrodotoxin (TTX), suggesting that they represented voltage-gated Na+ currents (INa). Activation curves were characterized with a V0.5 = -16.6 +/- 2.4 mV and a slope factor k = -5.2 +/- 0.2 mV while inactivation curves were characterized with a V0.5 = -60.9 +/- 1.7 mV and a slope factor k = 8.8 +/- 0.4 mV. Lowering external [Ca2+] to zero increased the maximum INa, shifted its voltage dependence in the hyperpolarizing direction and increased the rate of INa inactivation. Increasing external [Ca2+] or [Mg2+]decreased INa and slowed its rate of inactivation. These studies demonstrate the presence of voltage-gated Na+ channels with high TTX sensitivity that are modulated by extracellular divalent cations in human aortic smooth muscle cells maintained in cell culture. Window currents were found in the voltage range of -50 to -20 mV, suggesting that these channels could contribute to the resting membrane potential.

Calcium↗
PubMedDate not supplied

Basis for the altered arterial wall mechanics in the spontaneously hypertensive rat.

Carotid and tail arteries from 20-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were used to compare mechanics and biochemical properties. Measurements of pressure-diameter relations were made on isolated segments under conditions of active (145 mM K+) and passive (O mM Ca+2 and 2 mM EGTA) smooth muscle. Connective tissue, water and electrolyte contents, and extracellular water spaces were determined. Chemical data were also obtained from segments of thoracic aorta. The passive mechanics of arteries from the SHR were stiffer compared to those from WKY. Total connective tissue content (collagen + elastin) and collagen/elastin ratio were both smaller in the SHR arteries. Differences in the characteristics of the connective tissue matrix other than total content must exist in SHR and WKY arteries. Maximum values of active stress (force/area) developed by SHR arteries were larger and occurred at smaller values of wall strain compared to WKY arteries. The maximum reduction in wall diameter with smooth muscle activation was larger in the WKY arteries, but these constriction responses were better maintained at higher pressures by SHR arteries. Extracellular water space was lower in SHR arteries, while total water content was not different. The fraction of the wall of SHR arteries occupied by smooth muscle cells was larger than that of WKY arteries. When values of maximum active stress were normalized to the relative cell content, no difference was found for SHR and WKY carotids, but SHR tail arteries still produced a significantly larger active cell stress than WKY tail arteries. This suggests that intrinsic differences exist in the properties of smooth muscle cells of SHR and WKY tail arteries.

Animals↗
PubMedDate not supplied

Time course of arterial wall changes with DOCA plus salt hypertension in the rat.

Segments of carotid and tail artery, and thoracic aorta from control and hypertensive animals (DOCA + salt) were used for the study of mechanics and/or chemical composition. Pressure-diameter measurements were made on intact segments under conditions of active (145 mM-K+) and passive (O-Ca++ and 2 mM-EGTA) smooth muscle. Segments were used for chemical analyses of connective tissue content, water spaces, and electrolyte content. The passive stiffness of carotid and tail arteries increased monotonically with time. The carotids showed significant changes after two weeks of hypertension while the tail arteries only after 12 weeks. The collagen and total connective tissue content of the hypertensive arteries was decreased while collagen/elastin was unchanged. Smooth muscle activation produced larger changes in diameter of hypertensive arteries especially at higher values of transmural pressure. Maximum active force development was increased in carotid arteries at each time period from +2 weeks on while it was increased for the tail arteries only at +2 and +4 weeks. Relative cellular volume of these arteries was monotonically increased with hypertension. Maximum active force normalized to cellular content was not significantly different for carotid arteries from control and DOCA rats. For hypertensive tail arteries normalized on this basis force development remained elevated at +4 weeks but was significantly reduced at +12 weeks. Not all of the response to smooth muscle activation are monotonic with duration of hypertension, nor can all of these changes be explained on the basis of changes in cellular volume.

Animals↗