Intrastrain difference in serotonin and norepinephrine in discrete areas of rat brain.

Determination of levels of serotonin and norepinephrine in various brain areas of male Sprague-Dawley rats obtained from four different breeder-suppliers showed considerably different basal levels among the various groups, as well as differences in response to monoamine oxidase inhibitors.

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.

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.

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.

Effects of age on Ca2+ currents in small mesenteric artery myocytes from Wistar-Kyoto and spontaneously hypertensive rats.

The purpose of this study was to test the hypothesis that differences in voltage-gated Ca2+ channels increase with age during the development of sustained hypertension in the spontaneously hypertensive rat (SHR). Using patch-clamp methods, we measured whole-cell Ca2+ currents in freshly isolated myocytes from small mesenteric arteries of juvenile (5 to 7 weeks), young (10 to 12 weeks), and mature (19 to 23 weeks) Wistar-Kyoto rats (WKY) and SHR. Indirect tail artery systolic pressure increased progressively with age in SHR (from 125 +/- 5 to 159 +/- 5 to 192 +/- 5 mm Hg) but only in the younger WKY (from 107 +/- 6 to 130 +/- 4 to 136 +/- 4 mm Hg). Peak Ca2+ current density (current per cell capacitance) was larger in SHR than WKY myocytes at all ages (at 6 weeks, 3.5 +/- 0.4 versus 2.3 +/- 0.2 pA/pF; at 12 weeks, 3.8 +/- 0.2 versus 3.1 +/- 0.2; at 20 weeks. 4.9 +/- 0.4 versus 3.3 +/- 0.4). Cell capacitance (surface area) was significantly smaller in 12-week-old SHR than WKY (25.2 +/- 1.1 versus 31.8 +/- 1.6 pF), but no differences were found in the 6- or 20-week-old groups. There were significant differences in Ca2+ current with strain, age, and voltage but no significant age-strain interactions. The ratio of peak Ca2+ current for SHR to that of WKY declined linearly with voltage at all ages suggesting differences in the voltage dependence of Ca2+ current activation. The voltage dependence of Ca2+ current was shifted to the left in SHR compared with WKY at all ages. Activation curves were shifted significantly in the negative-voltage direction only in 20-week-old SHR myocytes. We have found differences with age in Ca2+ current density and its voltage dependence in SHR compared with WKY during the phase of development in which blood pressure becomes established in the SHR. The net effect of these differences predicts a larger Ca2+ current in SHR at voltages in the physiological range of membrane potential.

Augmented calcium currents in mesenteric artery branches of the spontaneously hypertensive rat.

The greater efficacy of organic channel blockers in lowering peripheral resistance and blood pressure in hypertensive subjects has been suggested to be the result of augmented calcium influx through L-type calcium channels in arterial smooth muscle. These studies were performed to determine whether differences exist in voltage-gated calcium channels of mesenteric artery branches from 20-week-old spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). Single myocytes were acutely isolated by collagenase and elastase treatment and studied at room temperature (approximately 20 degrees C) with the use of whole-cell, patch-clamp methods. Maximum values of calcium current measured at 0 mV from a holding potential of -90 mV were larger in SHR myocytes (105 +/- 11 versus 149 +/- 15 pA). Values of cell capacitance were smaller in SHR (29.5 +/- 1.3 pF) compared with WKY (35.0 +/- 1.5 pF) myocytes. Cell capacitance measures surface membrane area and, when used to normalize calcium currents, magnified the difference between WKY and SHR to approximately 47%. There was a larger percent reduction of maximum calcium current at holding potentials of -60 and -40 mV in SHR compared with WKY myocytes: for example, at -40 mV calcium current was reduced from values at -90 mV by -73 +/- 2% in SHR compared with -58 +/- 1% in WKY. When divided by the maximum current for each holding potential, the voltage dependence of normalized calcium currents for the two groups was completely superimposed. Difference currents were calculated by subtracting currents measured from holding potentials of -90 and -40 mV. The voltage dependence of difference currents was identical to that of the calcium currents measured from the two values of holding potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise training attenuates stress-induced hypertension in the rat.

The ability of exercise training to block the generation of hypertension produced by chronic stress in the borderline hypertensive rat was tested. Twenty-three male borderline hypertensive rats, F1 offspring of spontaneously hypertensive and Wistar-Kyoto rats, were divided into three groups. Two groups (8 rats per group) were subjected to 2 hours of daily, predictable, uncontrollable tail shock for 12 weeks. One of these groups was also given 2 hours of daily swim stress (exercise trained). A third group served as a maturation control and received neither intervention (n = 7). After 12 weeks of stress, direct recording of blood pressure verified the pattern observed with tail cuff: shock only group, 180/118 +/- 3/3 mm Hg; exercise-trained and shocked group, 166/108 +/- 4/2 mm Hg; and control group, 160/98 +/- 6/4 mm Hg (mean +/- SEM). Systolic and diastolic blood pressures in the shock only group were significantly higher than in both the other groups (p less than 0.05). The control group differed from the exercise-trained and shocked group only in diastolic BP (p less than 0.05). During a short-term stress session plasma norepinephrine levels in the exercise-trained and shocked group were significantly lower than those in the shock only group (555 +/- 56 vs 776 +/- 84 pg/ml; p less than 0.05). These results indicate that an alteration of autonomic function resulted from the exercise training, but its contribution to the resistance of the exercise-trained and shocked rats to stress-induced hypertension is unclear.

Characteristics of arterial myosin in experimental renal hypertension in the dog.

We compared myosin samples isolated from iliac-femoral arteries of control and renal (stenosis) hypertensive dogs to determine the effects of increased blood pressure on the characteristics of the myosin. The ratio of 204-kd (SM-1) to 200-kd (SM-2) myosin heavy chains was approximately 1:0.75 for myosin from the iliac-femoral artery of normotensive dogs. This was not altered significantly in response to hypertension. Both SM-1 and SM-2 myosin heavy chains cross-reacted with antibody against smooth muscle myosin on Western blot analysis. In addition to these heavy chains, purified myosin from both groups showed a very faint protein band slightly below the 200-kd myosin heavy chain on electrophoresis on a highly porous sodium dodecyl sulfate-polyacrylamide gel. This protein band cross-reacted with antibody against nonmuscle myosin but not with smooth muscle myosin antibody. The 20- and 17-kd light chains of myosin isolated from normotensive and hypertensive dogs gave similar results on isoelectric focusing. Peptide maps of tryptic digests of heavy chains revealed both quantitative and qualitative differences. The Ca(2+)-activated myosin ATPase activity measured in high salt (0.5 mol/L KCl) was similar for myosin from both groups, whereas the potassium (ethylenedinitrilo)tetraacetic acid-stimulated ATPase of myosin from hypertensive animals was higher than that from normotensive animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-related changes in arterial wall mechanics and composition of NIA Fischer rats.

Segments of carotid and tail arteries and descending thoracic aorta were obtained from the NIA colony of Fischer rats at ages 3, 12, 24 and 30 months. Measurements of pressure and diameter were made on intact cylindrical segments under conditions of active (147 mM K+) and passive (Ca2+-free and 2 mM EGTA) smooth muscle. These data were used to compute active and passive mechanics. Contiguous segments were used for the analysis of connective tissue, water and electrolyte contents. Passive stiffness of the carotid and tail arteries increased monotonically with increasing age. Collagen content in the aorta and tail artery generally increased with age, while elastin content decreased in the aorta and carotid artery. The ratio of collagen to elastin increased at all sites with age. Maximum values of active stress response (force development) increased from 3 to 12 months for the carotid artery, but decreased with age (at 24 and 30 months compared to 3 and 12-months) for the tail artery. Changes in relative cell content were such that active cellular force development was the same at all ages for the carotid artery but was smaller at 24 and 30 months compared to the younger animals for the tail artery. Decreased cellular force development by arterial smooth muscle is not an anatomically uniform finding in this animal model.

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.

The effects of intracerebroventricular injection of clonidine on conditioned pressor and adrenergic responses in rats.

Studies from this laboratory have shown that the first filial offspring of female spontaneously-hypertensive rats and male Wistar-Kyoto (WKY) normotensive rats develop stress-induced hypertension. The present study sought to examine the effects of intracerebroventricular administration of clonidine (8 micrograms) on cardiovascular and sympathoadrenal responses to aversive classical conditioning in these borderline hypertensive rats (BHR) and in normotensive WKY control rats. Clonidine caused significant reductions in resting arterial pressure, vascular resistance, heart rate and concentrations of epinephrine (E) in plasma for both hypertensive and normotensive rats. Central administration of normal saline to control rats of each strain did not alter basal cardiovascular or sympathoadrenal function. The presentation of a conditioned stimulus (CS) elicited a significant increase in arterial pressure and total peripheral resistance in hypertensive rats treated with saline and clonidine and in normotensive rats treated with saline. In contrast, normotensive rats treated with clonidine showed no increases in arterial pressure or vascular resistance following the onset of the conditioned stimulus. The aversive conditioning session instigated significant increases in the concentrations of norepinephrine (NE) and E in plasma in saline-treated rats. Hypertensive and normotensive rats treated with clonidine-showed a blunted increase in plasma concentrations of NE and E during this period; however, concentrations of E in hypertensive rats increased significantly from the baseline period after injection. These data suggest that an abnormality in central alpha 2-adrenoceptor-mediated inhibition of sympathoadrenal discharge and sympathetic vasomotor tone may predispose the hypertensive rat to develop stress-induced hypertension.

Contribution of salt to arterial wall changes in DOCA hypertension in the rat.

The contribution of drinking fluid salt to the development of deoxycorticosterone (DOCA) hypertension and arterial wall changes was assessed in unilaterally nephrectomized rats. Half of the DOCA-treated animals received saline supplemented with 0.2% KCl and the other half received deionized water as drinking fluid. All animals were fed standard rat chow (Na content = 0.36%). After 8 weeks, arterial pressures were significantly elevated in both DOCA groups to values which were not significantly different. The heart weight to body weight ratio was also elevated in both DOCA groups with a larger response in the saline-treated ones. Body weight of saline-treated DOCA rats was significantly lower than untreated controls and water-treated DOCA rats. Arteries from both DOCA groups exhibited increased passive stiffness, larger maximum active stress, wall thickening, decreased collagen and elastin concentration, greater relative cell volume, and greater water and cation concentrations. Larger changes were generally found in the saline- than the water-treated group. These results show that saline administration is not necessary for the development of hypertension or hypertension-induced arterial wall changes in DOCA-treated, uninephrectomized rats. Hypertension developed more slowly and arterial wall changes were similar in magnitude in water-treated animals. These results suggest that the rate and/or time history of pressure elevation may be an important factor contributing to hypertension-related arterial changes.

Effects of deoxycorticosterone on arterial wall properties in two-kidney rats.

The contribution of deoxycorticosterone acetate (DOCA) and salt to arterial pressure and hypertension-related arterial wall changes was assessed in Wistar rats. One group of two-kidney DOCA-treated animals was given a high salt diet and another group a low salt diet. After 16 weeks of treatment, the animals on low salt intake did not exhibit a significant increase in arterial pressure compared with untreated controls, while pressure was significantly elevated in the high-salt group. Values for the latter group were not as high as values in one-kidney, high salt DOCA-treated animals. Segments of the carotid and tail arteries were used for mechanical and chemical studies. Data obtained using arteries from the low salt two-kidney DOCA group were not significantly different from those of untreated controls. A number of significant differences were found in the two high salt groups compared with the low salt group and untreated controls; these included cardiac hypertrophy, increased passive arterial stiffness, decreased connective tissue concentration and increased maximum force development in response to high potassium plus norepinephrine activation. Larger changes were found in one-kidney compared to two-kidney DOCA animals. Thus DOCA administration to two-kidney rats on high salt intake produces moderate arterial hypertension and hypertension-related arterial wall changes. On the other hand DOCA administration to two-kidney rats on low salt intake does not produce an increase in arterial pressure nor altered arterial wall properties. These results suggest that DOCA in the absence of salt excess does not elevate arterial pressure or produce arterial wall changes.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Effect of thoracotomy upon the carotid sinus control of regional hemodynamics in the dog.

The effects of bilateral thoracotomy upon the operating characteristics of the carotid sinus reflex were examined in 11 vagotomized dogs. Pressure-flow relationships in the aorta, celiac, mesenteric, renal, and femoral arteries were studied as a function of pressure in the isolated carotid sinuses. These relationships were analyzed to give the carotid sinus reflex operating point values and sensitivities of pressure, flow, impedance, and power for each regional vascular bed. Following thoracotomy there was a significant fall in the closed-loop operating point pressure (CLOP) ( p less than 0.005). The operating point values and sensitivities for each regional flow and resistance together with the corresponding mean and oscillatory kinetic and pressure power were not significantly altered by thoracotomy. Renal characteristic impedance at the operating point significantly increased following thoracotomy (p less than 0.05), as did the aortic characteristic impedance for carotid sinus pressures (CSP) above the closed-loop operating point. The operating sensitivity of renal characteristic impedance was decreased (p less than 0.05). Possible mechanisms underlying these changes are discussed.

Comparison of K+ channel properties in freshly isolated myocytes from thoracic aorta of WKY and SHR.

Altered function of smooth muscle cell K+ channels have been reported in hypertension, but the contribution of various K+ channel types to these changes has not been completely determined. The purpose of this study was to compare the contribution of K+ channel types to whole cell K+ currents recorded from isolated thoracic aorta myocytes of 13 to 15 week old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Cells were isolated by collagenase and elastase digestion, and K+ currents recorded using whole cell voltage clamp methods at room temperature. Cells were superfused with a solution containing (in mmol/ L) 140 NaCl, 5 KCl, 2 CaCl2, 1 MgCl2, 10 HEPES, and 10 glucose. Pipettes were filled with a solution containing (in mmol/L) 120 KCl, 5 NaCl, 5 MgATP, 20 HEPES, and 10 BAPTA. The K+ currents (IK) recorded from a holding potential (HP) of -80 mV were smaller in the SHR compared to those in WKY (for example, at 20 mV: WKY = 6.1 +/- 0.6 pA/pF and SHR = 3.7 +/- 0.2 pA/pF). Values of cell capacitance were not different between the two groups (WKY = 25.2 +/- 3.2 pF and SHR = 26.6 +/- 1.9 pF). A component of IK inhibited by voltage (Kv) over the range from -80 to -20 mV was smaller in SHR. The voltage dependence of Kv availability and activation were not significantly different between the two groups. IK recorded from a HP = -20 mV (KCa) was not different between the two groups. Difference currents calculated from IK measured at HP of -80 and -20 mV (that is, Kv) were smaller in SHR as was the fraction of IK inhibited by 4-aminopyridine. These results suggest that under conditions of low intracellular [Ca2+] there are no differences in KCa currents, but the Kv currents are smaller in SHR. Inhibition of Kv by 4-aminopyridine (0.1 to 10 mmol/L) caused larger increases in basal tone in WKY aorta. These results suggest that Kv channels contribute to resting K+ conductance in both WKY and SHR aorta, but with a relatively larger contribution in the WKY.

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.

Augmented contributions of voltage-gated Ca2+ channels to contractile responses in spontaneously hypertensive rat mesenteric arteries.

The observation that organic Ca2+ channel blockers are more effective in lowering blood pressure and peripheral resistance in hypertensive compared to normotensive subjects suggests that there is a greater contribution from voltage-gated Ca2+ channels (CaL) to vascular force maintenance in hypertensive arteries. This study tests this hypothesis by comparing the effects of Bay k 8644 and nisoldipine on basal force development, contractile responses to norepinephrine and serotonin, and Ca2+ currents (ICa) in mesenteric artery (MA) from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). MA rings were used to record isometric contractions at Lmax. Single cells were isolated by collagenase plus elastase for measurement of CaL properties by patch-clamp methods. Contractile responses to Bay k 8644 were larger and more sensitive in SHR than WKY, and were larger in endothelium-denuded compared to intact rings. In SHR, the addition of 10 nmol/L Bay k 8644 increased contractile sensitivity to norepinephrine (NE) and serotonin (5HT), and increased maximum response to 5HT. In WKY, 10 nmol/L Bay k 8644 produced a small increase in 5HT sensitivity with no effect on maximum response, and had no effect on NE responses. In the presence of 1 mumol/L nisoldipine, the maximum response and the sensitivity to both NE and 5HT were decreased in both WKY and SHR with the inhibitory effects of nisoldipine being larger in SHR than WKY. Peak ICa was larger in SHR, and current-voltage curves were shifted toward more negative voltages compared to WKY. Bay k 8644 increased ICa in both WKY and SHR myocytes with no apparent difference in the magnitude of its effect when expressed as a percent of control ICa. These results suggest that CaL contribute significantly to tonic force maintenance as well as to agonist responses in MA from both WKY and SHR, but with a much larger contribution in SHR. Differences in the sensitivity of CaL to Bay k 8644 were not responsible for the differences in contractile responses to this agonist.

Differences in K+ current components in mesenteric artery myocytes from WKY and SHR.

Previous studies have documented increased K+ permeability of arterial smooth muscle in hypertension and suggested a role in altered arterial contractile function. To characterize the mechanisms responsible for these alterations, we determined the contribution of K+ current (IK) components to whole cell IK in freshly dispersed myocytes and tetraethylammonium (TEA)-induced contractile responses in mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Tetraethylammonium produced a larger tonic contractile response in SHR with a lower threshold compared to WKY (ie, 0.1 v 1 mmol/L), which was due in part to the larger Ca2+ current in SHR. Whole cell IK recorded by perforated patch methods was similar at a holding potential (HP) of -60 mV (IK60), but were larger in SHR when recorded from a HP of -20 mV (IK20). The selective blocker iberiotoxin (IbTX) was used to separate the contribution of voltage- (Kv) and calcium-dependent (KCa) components of IK60. The IK60 and IK20 component inhibited by 100 nmol/L IbTX (ie, KCa) was larger in SHR than in WKY myocytes, whereas the IbTX-insensitive IK60 component (ie, Kv) was larger in WKY. In the presence of IbTX, 1 and 10 mmol/L TEA inhibited a larger fraction of IK60 in SHR myocytes compared with WKY. The activation properties of the TEA-sensitive and TEA-insensitive Kv components determined by fitting a Boltzmann activation function to the current-voltage data, exhibited both group and treatment differences in the half maximal activation voltage (V0.5). The V0.5 of the TEA-sensitive Kv component was more positive than that of the TEA-insensitive component in both groups, and values for the V0.5 of both TEA-sensitive and TEA-insensitive components were more negative in SHR than WKY. These results show that SHR myocytes have larger KCa and smaller Kv current components compared with WKY. Furthermore, SHR myocytes have a larger TEA-sensitive Kv component. These differences may contribute to the differences in TEA contractions, resting membrane potential, Ca2+ influx, and KCa current reported in hypertensive arteries.

Baroreceptor control of pressure-flow relationships during hypoxemia.

In the absence of peripheral chemoreceptors, the effects of graded hypoxemia on the carotid sinus control of central and regional hemodynamics were studied in anesthetized mongrel dogs. Baroreceptor stimulation was effected by carotid sinus isolation and perfusion under controlled pressure. Blood flows were measured in the aorta and the celiac, mesenteric, left renal, and right iliac arteries. Carotid sinus reflex set-point pressures were well maintained until hypoxemia was severe. Carotid sinus reflex set-point gain was maximal during mild hypoxemia. Reflex operating point regional flows were unaffected by hypoxemia. A factorial analysis of overall reflex increases in mean aortic pressure, flow, and power during reduced baroreceptor stimulation showed potentiation by increasing hypoxemia. Corresponding effects of baroreceptor stimulation and hypoxemia on aortic resistance and heart rate were additive. Celiac, renal, and iliac blood flows increased during both hypoxemia and reduced baroreceptor stimulation. Only in the celiac bed were blood flow changes independent of concomitant changes in cardiac output. Thus, at maximum sympathetic stimulation (low carotid sinus pressure) during hypoxemia, the cardiovascular system maintained both central and regional blood flows at high systemic blood pressures independent of the peripheral chemoreceptors.