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R H Cox

Publications and source records attributed to R H Cox.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effects of putative K+ channel activator BRL-34915 on arterial contraction and 86Rb efflux.

Segments of thoracic aorta, mesenteric and tail arteries from male Wistar rats were used for the determination of isometric relaxation responses to BRL-34915 [chromakalin or (+/-)-6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl )-2H-benzo- [b]-pyran-3-ol] after contraction with half-maximal (ED50) values of norepinephrine or high K(+)-physiological salt solution. Contiguous segments were incubated in the presence of 86Rb and used for study of the effects of BRL-34915 on 86Rb efflux. BRL-34915 produced a dose-dependent relaxation of norepinephrine- or K(+)-induced active stress that was essentially complete (100%) in the aorta and mesenteric artery but only partial (30-40%) in the tail artery. The ED50 value of BRL-34915 for relaxation responses was about 0.1 to 0.3 microM. BRL-34915 had no significant sustained effect on 86Rb efflux from the tail artery or mesenteric artery branches but produced a dose-dependent sustained increase in efflux from thoracic aorta and portal vein. Responses reached a peak effect in 2 to 4 min after exposure but subsequently declined over a slower time course. Efflux responses to BRL-34915 had peak values that averaged 100 to 150% above basal levels with an ED50 value of about 1 to 3 microM. This suggests a dissociation of the effects of BRL-34915 in relaxation and efflux experiments. Treatment with 30 microM BRL-34915 decreased both the initial and sustained components of the subsequent 86Rb efflux response to 10 microM norepinephrine in both thoracic aorta and tail artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Altered agonist-activated 86Rb+ efflux from arteries in canine renal hypertension.

Basal rate constants for 86Rb+ efflux from renal arteries of renal hypertensive dogs were lower than those of control animals whereas no differences were found for coronary arteries. Norepinephrine produced parallel increases in efflux rate constants for hypertensive and control renal arteries, but serotonin produced smaller responses in hypertensive compared to control coronary arteries.

Animals↗
PubMed1989

Mutual interaction of vasoconstriction and endothelial damage in stenotic arteries.

Coronary artery vasomotion may be important in the pathogenesis of angina pectoris. Numerous experimental studies demonstrated accentuated arterial vasomotion in endothelium-damaged vessels. We examined interactions of stenosis, arterial vasoconstriction, and endothelium denudation in a stenosed artery preparation in vitro. Canine carotid arteries and porcine coronary arteries were perfused with a physiological salt solution under constant pressure and a fixed distal resistance. Pressures at the proximal and distal ends of the artery, as well as the flow, were continuously recorded. Hemodynamic responses to serotonin, norepinephrine, and angiotensin II were separately studied. In intact arteries without stenosis, the agonists produced a 30-40% reduction in lumen diameter without altering flow or distal pressure. After a luminal stenosis was created, vasoconstriction produced by the agonists decreased flow and increased the pressure gradient across the stenosis. Flow decreased to (or near) zero, indicating occlusion at the stenotic site. After endothelial loss, this effect was amplified, demonstrating occlusion of the artery and suppression of the flow at significantly (P less than 0.05) lower concentrations of agonist (0.1-0.3) compared with endothelial intact arteries. These studies illustrate 1) the necessity for the presence of stenosis in large arteries for vasoconstriction to impair flow and 2) the protecting effect of intact endothelium in blunting the effects of arterial vasoconstriction in stenosed vessels. Through the reciprocal interaction of arterial stenosis, vasoconstriction, and endothelial damage, ischemic events associated with certain types of vasomotion can be explained.

Angiotensin II↗
PubMed1989

Effects of aging on agonist-activated 86Rb efflux in arteries of Fischer 344 rats.

Segments of thoracic aorta (DTA), tail artery (TA), and mesenteric artery branches (MAB) were obtained from male Fischer 344 rats at ages of 1, 2, 6, 12, 24, and 30 mo and were used to determine the effects of aging on agonist-activated 86Rb (and 42K) efflux. At all three arterial sites, basal efflux decreased during development (1-6 mo), but no further changes were observed with aging (6-30 mo). The initial efflux response to 10 microM norepinephrine (NE) in the presence of 1 microM propranolol exhibited either no change (DTA) or an increase (TA and MAB) during development (1-6 mo), but all three sites showed a large decrease during aging (6-30 mo). Changes in the steady-state response to NE paralleled changes in the basal efflux at all ages and arterial sites. The initial efflux response to 75 mM K+-physiological salt solution (PSS) for the DTA in the presence of 1 microM phentolamine and 1 microM propranolol decreased during development followed by an increase during aging, whereas for the TA and MAB, there were no significant changes with age. The steady-state efflux response to K+ decreased during development at all three sites but was increased only for the DTA during aging. The steady-state efflux response to K+ was not altered for the TA and MAB during aging. Efflux responses using 42K were qualitatively similar, but rate constants were quantitatively larger than those with 86Rb at all three arterial sites and at all ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1989

Effects of endothelium regeneration on canine coronary artery function.

During coronary catheterization under general anesthesia, the endothelium of a portion of the proximal left circumflex coronary artery of dogs was removed (injured). Segments from the denuded and normal (distal circumflex and left anterior descending coronary) regions were removed immediately in some animals (acute studies) or 5 wk after the injury in other animals (chronic studies). No significant differences in passive mechanics or active stress normalized to medial thickness were found between segments from normal and denuded regions in acute studies or normal and injured segments in chronic studies. Intimal thickening was found in the chronically injured segments, which averaged 32% of the total media-adventitia thickness. No significant differences were found in potassium dose-response relations in acute or chronic studies. Maximum responses to serotonin were increased in acutely denuded but not in chronically injured segments. Sensitivity to serotonin was increased in chronically injured but not acutely denuded segments. Endothelium-dependent relaxation responses produced by acetylcholine, bradykinin, and the Ca2+ ionophore A23187 were all depressed in chronically injured segments compared with normal, as were relaxation responses to sodium nitroprusside. In acutely denuded segments, the former agents produced only small contractions at high doses, whereas nitroprusside relaxations were augmented compared with sites with intact endothelium. Relaxation responses to isoproterenol and forskolin were not significantly affected by acute denudation or by chronic injury. The results of this study suggest a "chronic" depression of relaxation responses mediated by the guanosine 3',5'-cyclic monophosphate pathway and increased serotonin vasoconstriction sensitivity in arteries 5 wk after an endothelial denudation injury.

Animals↗
PubMed1989

Bilateral renal denervation can prevent the development of stress-induced hypertension in the borderline hypertensive rat.

The borderline hypertensive rat (BHR) shows large blood pressure responses to either stress or a high salt diet. Since the renal nerves have been shown to play a role in several animal models of hypertension, the current study sought to determine the effect of bilateral renal denervation on the development of stress-induced hypertension in the BHR. BHR were deprived of renal nerves under ether anesthesia after either 5 or 11 weeks of daily 2-hour stress sessions. Additional BHR received sham surgery. Unstressed BHR, age-matched to stressed groups, received denervation or sham surgery. Following a 3 week recovery period, the protocol (stress or no stress) was continued for 10 additional weeks. Tail cuff systolic blood pressures were obtained weekly. BHR stressed for 5 weeks prior to denervation failed to develop hypertension in response to continued stress. Although BHR stressed for 11 weeks prior to denervation showed a temporary reduction in pressure following denervation, blood pressure returned to the hypertensive levels of sham-operated controls after several weeks. Thus, there may be a critical period during which the renal nerves are necessary for the expression of stress-induced hypertension in the BHR. These observations are discussed in relation to the effects of renal denervation on hypertension in various animal models.

Animals↗
PubMed1989

Psychomotor screening for USAF pilot candidates: selecting a valid criterion.

Subjects for this research were 153 prospective pilots who were tested on computerized versions of the Two Hand Coordination (2HC) and Complex Coordination (CC) psychomotor tests. Independent variables included five basic error scores associated with the two psychomotor tests. The criterion for pilot performance was conceptualized as a function of the number of flying hours required to graduate from Undergraduate Pilot Training (UPTFLY). Results of MANOVA and multiple regression analyses revealed that performance on the two psychomotor tests was significantly related to the criterion for pilot performance (UPTFLY). The multiple regression analysis resulted in 27.1% of the variability of UPTFLY being accounted for by psychomotor performance. When the data were reanalyzed using a pass/fail UPT criterion the variability accounted for remained high, suggesting an anomaly associated with sample selection. Undergraduate pilot training outcome (pass/fail) remains the most valid criterion for Undergraduate Pilot Training success.

Adult↗
PubMed1988

Altered Na+-K+-ATPase, cell Na+ and lipid profiles in canine arterial wall with chronic cigarette smoking.

1. We evaluated the influence of cigarette smoking on arterial wall membranes, using Na+-K+-ATPase activity, free cholesterol (FC) and phospholipid (PL) contents as indices of membrane structural and functional integrity. 2. Segments of aorta, carotid and femoral arteries were obtained from normal dogs (controls) and dogs subjected to chronic cigarette smoking for 2 yr (12 cigarettes a day). 3. Na+-K+-ATPase activity was assessed in segments of carotid and femoral arteries using a ouabain-sensitive 86Rb uptake procedure for intact tissues. 4. Free cholesterol and phospholipids were separated, identified, and quantitated from extracts of aortic samples by means of two dimensional thin-layer chromatography. 5. Na+-K+-ATPase activity was reduced in the smoker group in both carotid and femoral arteries. This reduced enzyme activity was accompanied by a rise in cell Na+ levels at both arterial sites. 6. Aortic FC was elevated and the PL profile was altered in the smoker group; as a result, phosphatidylcholine was reduced, whereas lysophosphatidylcholine, phosphatidic acid, and cardiolipin were elevated. 7. Phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and sphingolipid levels were unchanged. In addition, the FC/PL ratio was increased in the smokers. 8. Taken together, the changes in Na+-K+-ATPase activity, FC/PL ratio and phospholipid profiles observed are consistent with the hypothesis that chronic cigarette smoking causes a reorganization of the phospholipid bilayer in the smooth-muscle cell membrane of the arterial wall.

Animals↗
PubMed1988

Lithium chloride stabilizes systolic blood pressure and increases adrenal catecholamines in the spontaneously hypertensive rat.

The effects of daily, intraperitoneal injections of LiCl (3 mEq/kg) on systolic blood pressure (SBP) and adrenal catecholamine levels were measured in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats (WKY). Control animals from each strain were injected with equivalent volumes (0.1 ml/100 g b.wt.) of 0.9% saline (0.15 mEq/kg). SBP in LiCl-treated SHR was significantly lower (p less than 0.05) than that of saline-treated SHR (177 +/- 7 vs. 196 +/- 4 mm Hg, respectively) after one week. After two weeks SBP was lower in LiCl SHR than in saline controls, but this difference was not significant. While SBP of both LiCl and saline treated WKY was not significantly different (146 +/- 4 vs. 147 +/- 8 mm Hg, respectively), SBP in both WKY groups remained lower than the SBP for either group of SHR. LiCl induced a significant weight loss in the SHR, but not in the WKY. Adrenal norepinephrine and epinephrine were significantly (p less than 0.05) higher in LiCl-treated rats of both strains; dopamine was also higher in LiCl-treated rats of both strains, but significant only between SHR-LiCl and SHR controls. It appears that LiCl's effect in slowing the development of hypertension is independent of its action on adrenal catecholamines. The SHR's increased sensitivity to LiCl, relative to weight loss and SBP, may reflect differences in genetic or physiological status of the animal compared to WKY. These differences may be associated with alterations in membrane ion transport systems.

Adrenal Medulla↗
PubMed1988

Comparison of arterial wall properties in young and old racing greyhounds.

Arteries were obtained from several sites in young (YGH) and old racing greyhounds (OGH). Segments were used for the determination of arterial wall mechanics under conditions of active (norepinephrine) and passive (Ca2+ free and 2 mM EGTA) smooth muscle. Contiguous segments were used for the chemical analysis of connective tissue, water and electrolyte content. The passive stiffness of arteries from OGH was consistently greater than that of the YGH. Collagen content and the collagen-elastin ratio were larger at all sites in the OGH. However, the connective tissue changes were not considered to be of sufficient magnitude to explain the changes in passive mechanics. Maximum values of active stress development were generally lower in arteries from the OGH as was their relative cell content. Active stress development normalized to smooth muscle cell cross-section was not uniformly changed in arteries from OGH. In spite of the lower active stress development in some arteries, the ability of smooth muscle to constrict lumen diameter was not different between OGH and YGH at transmural pressures in the physiological range. While a number of changes occur in arteries of purebred greyhounds with aging, they appear to occur in such a fashion that normal function is not grossly altered.

Aging↗
PubMed1988

The borderline hypertensive rat: a model for studying the mechanisms of environmentally induced hypertension.

The borderline hypertensive rat (BHR) is a first-generation cross between the spontaneously hypertensive rat and the normotensive Wistar-Kyoto rat. The BHR develops frank hypertension when chronically stressed or when fed a high-sodium diet. Stress-induced hypertension can be blocked by exercise. The role of the central nervous system and kidney in hypertension development in this model is discussed.

Animals↗
PubMed1988

Cardiovascular baroreceptor control during angiotensin-induced acute hypertension in the dog.

Central and regional cardiovascular responses to step changes in carotid sinus pressure were evaluated in dogs before and after increasing carotid sinus reflex set point pressure, by approximately 30%, via an intravenous infusion of angiotensin II at three anesthetic levels (isoflurane). With respect to overall cardiovascular behavior, angiotensin inhibited both the interaction of carotid sinus baroreceptor stimulation and anesthesia upon mean arterial pressure and total resistance, together with the inverse relationship between iliac resistance and carotid sinus pressure. At the set point pressure of the carotid sinus reflex, angiotensin increased set point levels of aortic, celiac, mesenteric and renal resistances, reduced corresponding set point flows, and increased the range of arterial pressure control together with the maximum capacity of the carotid sinus reflex to increase mean aortic pressure and power for all anesthetic levels. Angiotensin increased the set point sensitivity of mean arterial pressure (gain), heart rate, iliac blood flow, aortic, celiac, mesenteric and renal resistance, to changes in carotid sinus pressure for intermediate anesthetic levels. While reflex gain was unchanged by angiotensin, peak gain was significantly increased at lower anesthetic levels. The maximum capacity of the carotid sinus reflex to decrease mean aortic pressure and power was reduced. Thus, intravenous angiotensin infusion producing moderate increases in mean arterial pressure facilitates the ability of the carotid sinus baroreceptors to control mean arterial pressure and heart rate, and results in an increased overall vasoconstrictor capacity. Corresponding increased ability to control regional blood flow was confined to the iliac bed.

Acute Disease↗
PubMed1988

Baroreceptor control of central and regional hemodynamics with isoflurane in the dog.

Central and regional hemodynamics were studied at five levels of carotid sinus baroreceptor stimulation and three isoflurane levels. Apart from iliac blood flow, all regional blood flows, together with mean aortic pressure, power and flow decreased in response to an increasing anesthetic level and/or carotid sinus baroreceptor stimulation. These effects were additive with no significant interaction between the two experimental factors. At the carotid sinus reflex set point pressure, isoflurane attenuated the ability of carotid sinus baroreceptors to change mean aortic pressure and power together with the maximum capacity of the carotid sinus baroreceptors to produce vasoconstriction. The maximum capacity of the carotid sinus baroreceptors to produce vasodilation was unaffected by isoflurane. Vagotomy only modified hemodynamic set point values at low isoflurane levels, increasing regional resistances at the expense of flow except for the iliac bed. Following vagotomy, reflex gain was increased as was the maximum capacity of the cardiovascular system to vasoconstrict and vasodilate in response to carotid sinus pressure stimulation, together with the range of arterial pressure control.

Animals↗
PubMed1988

Cardiovascular and renal responses to stress in borderline hypertensive rat.

Wistar-Kyoto (WKY) and borderline hypertensive rats (BHR) were exposed to either a normal or high-sodium chloride (NaCl) diet for 8 wk. Cardiovascular and renal data were collected from arterial and bladder catheters, respectively, in conscious animals during control and stress (aversive classical conditioning) sessions. Results indicated that BHR on a high-NaCl diet exhibited no increase in blood pressure in response to stress compared with BHR on a normal diet. A high-NaCl diet diminished the recovery of blood pressure to base line during stress in WKY compared with normal NaCl controls. Also, a high-NaCl diet and stress interacted in the BHR to decrease sodium excretion and renal plasma flow during stress compared with the control session (3.8 vs. 4.8 mueq.min-1.100 g body wt-1; 3.6 vs. 4.0 ml.min-1. 100 g body wt-1, respectively). Finally, increased dietary NaCl blunted the norepinephrine response to stress in WKY but not in BHR (263 vs. 767 pg/ml). These data suggest that the interaction of genetic and environmental factors are important variables for the development of hypertension.

Animals↗
PubMed1988

Aerobic power and cardiovascular response to stress.

The relationship between aerobic fitness as measured by maximal O2 uptake (VO2max) and the cardiovascular response to laboratory stressors was examined in two experiments. First, 34 male college students were screened on the basis of their heart rate (HR) response to a reaction time-shock avoidance (RT-AV) task. The six individuals showing an average HR increase of 45 beats/min (reactives) and the six subjects showing an average increase of 8 beats/min (nonreactives) did not differ in VO2max (47.7 +/- 2 vs. 48.7 +/- 1 ml.kg-1.min-1, respectively). However, a statistically significant association between a reported family history of hypertension and peak HR response to RT-AV was seen. In the second series of experiments, the plasma catecholamine and cardiovascular responses of eight elite endurance-trained athletes (VO2max 70.6 +/- 1 ml.kg-1.min-1) and eight untrained volunteers (VO2max 45.5 +/- 1 ml.kg-1.min-1) were compared on the following: RT-AV, reaction time for monetary reward (RT-AP), cold pressor, isometric handgrip, and orthostatic challenge (standing). The trained group exhibited a significantly lower mean HR at rest (P less than 0.05), otherwise there were no significant differences between the two groups. The results indicate that although individual differences (e.g., family history of hypertension and high resting HR) can be related to the potential for cardiovascular responses to novel laboratory challenges, the contribution of fitness to this characteristic is much less clear. Further exploration of questions pertaining to fitness and stress should focus on individuals with a predisposition to stress reactivity.

Adult↗
PubMed1988

Effects of hypertension and its reversal on canine arterial wall properties.

Segments of carotid, femoral, saphenous, and left circumflex coronary arteries were obtained from control, renal hypertensive, and nephrectomized hypertensive dogs for in vitro study of mechanical properties. Hypertension was produced in two-kidney dogs by unilateral renal artery constriction. After 3 months, the compromised kidney was removed in half of the dogs. Mean arterial pressure was significantly elevated in the hypertensive dogs after 3 months (127 +/- 2 vs 94 +/- 1 mm Hg for controls) and partially returned toward normal 3 months after nephrectomy (105 +/- 2 mm Hg). Pressure-diameter relations were determined under conditions of maximum active and passive smooth muscle activation. Contiguous segments were used for the determination of water and connective tissue content. Hypertension was associated with increased passive arterial wall stiffness at most sites, with a partial return toward normal after nephrectomy. Maximum responses to smooth muscle activation (active stress and constriction response) were augmented in arteries from hypertensive dogs and partially returned toward normal in the nephrectomized hypertensive group. The elastin content of these arteries was unchanged, while collagen content was nonuniformly decreased in renal hypertensive dogs. Small decreases were found in the radius-wall thickness ratio of some arteries. No significant mechanical changes occurred in the saphenous artery. The largest hypertension-related changes were found in the coronary arteries, which also exhibited the smallest recovery toward normal properties after nephrectomy. Considerable regional variability of changes in arterial wall in renal hypertensive and nephrectomized hypertensive dogs was found. Incomplete resolution of the hypertension and arterial wall changes by nephrectomy was found in this animal model.

Animals↗
PubMed1988

Effects of chronic beta-aminoproprionitrile treatment on rat carotid artery.

The effects of chronic treatment of young rats (initially 8 weeks old) with the collagen cross-linking inhibitor, beta-aminoproprionitrile (BAPN), on arterial wall properties were studied. BAPN was added to the drinking water for 8 weeks to produce intakes of 0, 100, 200 and 400 mg/kg/day. Systolic pressure of treated animals did not increase with age as rapidly as that of untreated controls. Weight gain of treated animals was inhibited at the highest (BAPN) treatment level. Passive stiffness of isolated, cylindrical segments of carotid arteries was decreased in BAPN-treated animals in a dose-dependent manner. BAPN treatment had no significant effect on the total collagen or elastin content (hydroxyproline) of carotid arteries. Values of maximum active force development to 10 microM norepinephrine plus 75 mM K+ were decreased by BAPN treatment in a dose-dependent manner. There was no significant effect of BAPN treatment on total water content or its cellular and extracellular components in the carotid artery. The relative cell volume of carotid arteries was not altered by BAPN treatment, suggesting that the decreased force development was a characteristic of individual cells. These results suggest that BAPN treatment may decrease stiffness by altering secondary characteristics of the connective tissue matrix without affecting connective tissue content. The decreased maximum smooth muscle force development may be responsible for the blood pressure-lowering effects of BAPN.

Administration, Oral↗