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Biomedical subjects

D F Bohr

Publications and source records attributed to D F Bohr.

At least 37 records · Page 2Linked to original sources
PubMed1991

Mechanisms of calcium relaxation of vascular smooth muscle.

We examined mechanisms of relaxation in intact and endothelium-denuded thoracic aortic rings of rat in response to various concentrations of calcium (from 1.6 to 10.1 mM) after contraction induced by 30 mM KCl. The relaxation to calcium was concentration dependent in intact and denuded rings. This effect was greater in intact preparations than in denuded preparations or in intact preparations treated with methylene blue (10(-5) M). This indicates that the relaxation by calcium is partly mediated by releasing endothelium-derived relaxing factors (EDRFs). In the presence of A23187, the relaxation to calcium was attenuated in intact rings but not in denuded rings, whereas calcium relaxation was not significantly altered by sodium nitroprusside. These observations suggest that the calcium-induced relaxation is reduced if EDRF has already been released by A23187. We conclude that, paradoxically, the same increase in extracellular Ca2+ concentration that causes an increase in endothelial intracellular calcium concentration ([Ca2+]i) to produce EDRF also results in membrane stabilization of the vascular smooth muscle cell to decrease [Ca2+]i and cause relaxation. These two mechanisms are additive in producing calcium relaxation in the intact artery.

Acetylcholine↗
PubMed1991

Experimental hypertension.

Several interventions are used to induce hypertension in the experimental animal. The three most used interventions are renal ischemia, mineralocorticoid excess, and genetic manipulation. The sequence of events leading from these initiating manipulations to the elevated arterial pressure is being explored to define the mechanism responsible for hypertension. The following mechanisms are currently extensively evaluated: Pressor and depressor factors of renal origin, neurogenic regulation, circulating humoral factors, vessel wall hypertrophy, and membrane transport abnormality. The experimental models of hypertension hold great promise in providing an understanding of the mechanisms and developing effective treatment in clinical hypertension.

Animals↗
PubMed1991

Pathophysiology of the vasculature in hypertension.

The vessel wall is thicker in hypertension. Folkow demonstrated that adaptive structural changes occur in vessels in response to the increased wall stress of hypertension. Because the vessel wall thickens and encroaches on the lumen, the adaptive change results in an elevated vascular resistance. It also exaggerates the vasoconstrictor effects of vascular smooth muscle contraction, thereby increasing vascular reactivity to physiologically occurring vasoactive agents. As solid as this information may be, important unanswered questions still remain related to the question "What makes the pressure go up in the first place?" In this brief review, we have examined possible culprits both in the area of extrinsic vascular regulatory systems and in that of intrinsic changes in the vascular smooth muscle cell. Interesting newly described vasoactive agents currently are being evaluated. On the other hand, generalized intrinsic abnormalities in the cell membrane are well documented in hypertension. Many individual transport systems display this abnormality, suggesting that the primary defect may be in the lipid bilayer that influences the function of all integral protein transport systems. Abnormalities also have been found in the cells' signal transduction systems, whereas the energy metabolism and contractile protein system are essentially normal. Functional abnormalities of the vascular smooth muscle cell in hypertension must explain both its increased contraction and its increased growth. It is likely that the same functional abnormality may explain both of these changes.

Animals↗
PubMed1991

Lipid bilayer in genetic hypertension.

Membrane microviscosity, phospholipid composition, and turnover were measured in cultured vascular smooth muscle cells isolated from mesenteric arteries of stroke-prone spontaneously hypertensive and age-matched, normotensive Wistar-Kyoto rats. Membrane microviscosity, measured with fluorescence polarization, revealed greater microviscosity (lower fluidity) of the membranes isolated from smooth muscle cells from hypertensive as compared with those isolated from normotensive rats (p less than 0.01). Preincubation of membranes from hypertensive rats with 5 mM calcium reduced membrane microviscosity in "core" and in "surface" regions of the bilayer toward values observed in Wistar-Kyoto rats. Phospholipid composition did not differ between intact aortas and cultured mesenteric cells or between those tissues obtained from normotensive and from hypertensive rats. The total lipid-associated radioactivity was significantly lower in cells from stroke-prone spontaneously hypertensive rats than in those from Wistar-Kyoto controls (p less than 0.01). Phosphatidylcholine incorporated 70% and phosphatidylinositol 16% of total lipid-associated radioactivity, with no difference between cells from hypertensive and normotensive animals. Turnover of phosphatidylethanolamine was greater in cells from Wistar-Kyoto rats (p = 0.02), whereas turnover of phosphatidylserine was greater in cells from stroke-prone spontaneously hypertensive rats (p = 0.04). The greater microviscosity of the lipid bilayer in hypertension is a generalized defect of the matrix in which the transport proteins function. We hypothesize that this defect is responsible for the multiple abnormalities of membrane transport systems that have been described in genetic hypertension.

Animals↗
PubMed1990

Decreased activity of the sodium-calcium exchanger in tail artery of stroke-prone spontaneously hypertensive rats.

The ability of the Na-Ca exchanger to modify vascular relaxation was studied in rings isolated from tail arteries of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). The arteries were contracted with norepinephrine (NE) 1 microM and after stabilization they were transferred to a Ca-free physiological salt solution still in presence of NE. The time to 50% relaxation (T-50) in these conditions was significantly greater in SHRSP (78 +/- 7 s) than in WKY (50 +/- 7 s). When the calcium pump was stopped with vanadate (VAN), the Ca uptake by the sarcoplasmic reticulum with ryanodine (RY) and the Na-Ca exchanger with a Na-free PSS, the relaxation was slowed (T-50 increased to 198 +/- 16 s in SHRSP and to 162 +/- 14 s in WKY). Releasing the Na-Ca exchanger only (i.e. still with VAN and RY but with normal Na in the bath) the T-50 for relaxation in Ca-free PSS was, in WKY, nearly as fast as in control conditions (54 +/- 8 s). However, the Na-Ca exchanger in SHRSP was not so effective, and the T-50 for relaxation was slower than in control conditions (122 +/- 10 s). We conclude that the activity of the Na-Ca exchanger is depressed in tail arteries of SHRSP. This abnormality in resistance vessels, would contribute to the enhanced vascular tone present in hypertension.

Animals↗
PubMed1990

Calcium sensitivity of Ca2(+)-activated K+ channels in spontaneously hypertensive stroke-prone rats.

In previous studies, we measured a greater intracellular free calcium concentration and net potassium efflux, possibly calcium activated, in lymphocytes from spontaneously hypertensive stroke-prone rats (SHRSP) as compared with Wistar-Kyoto (WKY) rats. In this study, we addressed two related questions: 1) Can the greater intralymphocytic calcium concentration of the SHRSP account for the greater net potassium efflux? 2) Is the calcium sensitivity of calcium-activated potassium channels in lymphocytes from SHRSP different as compared with that of those from WKY rats? Ionomycin, a calcium ionophore, caused a concentration-dependent and proportional increase in net potassium efflux and intracellular free calcium concentration in lymphocytes from both strains of rat. Based on the relations between net potassium efflux and intracellular free calcium concentration established with ionomycin, the resting net potassium efflux of lymphocytes from SHRSP is greater than would be predicted based on the resting intracellular free calcium concentration. Using the patch clamp technique, we were able to identify and characterize a calcium-activated potassium channel in the plasma membrane of lymphocytes from both strains of rat. Potassium currents were recorded that had a slope conductance of 18.1 +/- 1.49, n = 6, and 18.5 +/- 1.44, n = 7, in WKY rat and SHRSP thymocytes, respectively. The channel exhibited rectification of the outward current in both strains of rat. Channels tended to appear in clusters of two or more per patch and were recorded in 30-50% of the patches examined. Calcium sensitivity of the channels was similar; maximum activation occurred at 700 nM free calcium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Role of endothelium in the response to endothelin in hypertension.

The relation between endothelin and acetylcholine (ACh) was examined and compared in aortas from Wistar-Kyoto (WKY) rats and from stroke-prone spontaneously hypertensive rats (SHRSP). The relaxation produced by ACh in an endothelin-induced contraction was less in aortas from WKY rats than in those from SHRSP. In aortas from WKY rats but not in those from SHRSP, the contraction produced by endothelin was augmented when the intact aortic rings were treated with methylene blue (10(-5) M). This augmentation was also found in preparations of the WKY rat aortic rings in which the endothelium had been removed. The augmentation was not present in SHRSP aortic rings that had been similarly denuded. Treatment with indomethacin (5 x 10(-6) M) had no effect on endothelin-induced contraction in either WKY rat or SHRSP aortic rings. Our findings indicate that endothelin and ACh have in common the ability to release endothelium-derived relaxing factor (EDRF) in WKY rat aortic rings. The reduced endothelium-dependent relaxation in response to ACh in the WKY rat probably reflects the fact that endothelin had already released the EDRF in rings from this strain of rats. The release of EDRF by endothelin is less in SHRSP than it is in WKY rats. Because of this failure of endothelin to release EDRF in SHRSP, endothelin may contribute to the increase in total peripheral resistance in this form of hypertension.

Acetylcholine↗
PubMed1989

Individualities in post-serotonin attenuation and Na+/K+ pump activity in vascular smooth muscle.

Prior treatment with serotonin (10(-8)-10(-7) M for 6 min) attenuated responses of rabbit mesenteric arteries to norepinephrine (NE) by 18-62%, but was without effect on the responses of the rabbit aorta. K+ relaxation responses in the mesenteric arteries were enhanced by serotonin, but in the aortic strips K+ relaxation occurred either before or after treatment with serotonin. Maximum relaxation to monensin was similar in the two tissues. Post-serotonin attenuation and K+ and monensin relaxation were blocked by ouabain, indicating that they depended on Na+/K+ pump stimulation. Intracellular Na+ contents (Nai) were determined in the vessels by the Li substitution method. Nai was greater, and was increased to a greater extent by serotonin and K(+)-free physiological salt solution in the mesenteric artery compared to the aorta, suggesting that the cell membrane of the mesenteric artery is leakier to Na+ than is that of the aorta. We conclude that the absence of post-serotonin attenuation in the aorta results from the failure of serotonin to increase Nai and thereby to stimulate the Na+/K+ pump in this tissue. This study demonstrates that important individualities in vascular smooth muscle reactivity even in the same animal may result from differences in membrane permeability to sodium.

Animals↗
PubMed1989

Lanthanum potentiation of the vascular response to a protein kinase C activator in genetically hypertensive rats.

The effects of lanthanum on the contraction induced by the protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA) were studied in femoral artery rings from stroke-prone, spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). When exposed to a calcium-free buffer containing 1 mmol/l EGTA, the femoral artery rings from SHRSP and WKY, pre-contracted with TPA (10(-6) mol/l), relaxed by 52 and 24%, respectively. Treatment of the rings in this calcium-free buffer with 2.6 mmol/l lanthanum significantly potentiated the TPA-induced contractions in vascular rings from WKY (49%) and SHRSP (136%). Potentiation by lanthanum of the TPA-induced contraction in the absence of extracellular calcium suggests that this cation is acting intracellularly to increase protein kinase C activity. The increased vascular responsiveness of SHRSP to lanthanum may reflect an abnormality in protein kinase C activation in vascular smooth muscle of genetically hypertensive rats.

Animals↗
PubMed1989

Central action of sodium chloride on whole body pressor responsiveness in the DOCA-treated rat.

This study investigated the effect of chronic intracerebroventricular (IVT) infusion of a hypertonic NaCl (400 mmol/l) artificial cerebrospinal fluid (aCSF) on blood pressure and whole body pressor responsiveness, in control rats (CH) and in rats implanted with deoxycorticosterone acetate (DOCA; DH). An isotonic aCSF was infused into another group of control (Cl) and DOCA (Dl) rats. Indirect systolic blood pressure (SBP) was measured using a tail-cuff technique once a week prior to and during the infusion period. Following 2 weeks of infusion, SBP increased significantly only in the DH and CH groups. In urethane-anaesthetized rats, the pressor response to intravenous infusions of norepinephrine and angiotensin II (Ang II) increased significantly in DH rats. When compared with Cl and Dl rats, those from the CH group also exhibited an enhanced response to norepinephrine and Ang II. However, this increase was not as great as in the DH animal. These results show that whole body pressor responses to norepinephrine and Ang II, increase in rats receiving chronic IVT infusion of hypertonic NaCl. These responses coincide with moderate but significant increases in SBP. These data indicate that sodium chloride acts at a central site to increase norepinephrine and Ang II pressor responsiveness in mineralocorticoid hypertension.

Angiotensin II↗
PubMed1989

Pressor responses to vasopressin in pigs and sheep with DOCA hypertension.

Pressor responses to vasopressin were determined in pigs and sheep during three experimental periods: 1) before deoxycorticosterone acetate (DOCA) treatment, 2) 21 days after DOCA implantation (100 mg/kg) when a stable hypertension had developed, and 3) after reversal of the hypertension by removing the implant in the sheep or by decreasing the dietary sodium intake in the pigs. The infusion of lysine (LVP) or arginine (AVP) vasopressin into pigs and sheep, respectively, resulted in dose-dependent increases in plasma vasopressin concentration. The levels of plasma LVP or AVP achieved by these infusions were not altered in any of the experimental periods. The administration of vasopressin resulted in dose-dependent increases in mean arterial blood pressure. However, pigs required five times more LVP than sheep required AVP to achieve similar pressor responses. The pressor responsiveness to vasopressin was attenuated when either species was made hypertensive. This effect was reversed when normal blood pressure was restored by reducing sodium intake in the pigs or by removing the DOCA implant from the sheep. These data establish that an increased pressor response to vasopressin does not contribute to DOCA hypertension in pigs or sheep.

Animals↗
PubMed1989

Potassium-induced relaxation of arteries in hypertension: modulation by extracellular calcium.

Smooth muscle relaxation due to activation of Na+-K+-adenosinetriphosphatase (ATPase) (K+ relaxation) was studied in isolated tail arteries from stroke-prone spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rats. Exposure to K+ (7 mM) relaxed a norepinephrine (1 microM) contraction induced in K+-free physiological salt solution (PSS) by 46 +/- 3% in WKY and by 81 +/- 3% in SHRSP. Incubation with monensin (10 microM) augmented the K+-relaxation in WKY to 61 +/- 5%. Incubation with amiloride (10 microM) or with low-Na+ (10 mM) PSS attenuated the K+ relaxation in SHRSP to 34 +/- 3 and 5 +/- 2%, respectively. Incubation with high-Ca2+ (6.6 mM) PSS attenuated the K+ relaxation in WKY to 25 +/- 3% but resulted in only a slight decrease in the relaxation in SHRSP (to 73 +/- 2%). We conclude 1) that a greater Na+ leakiness of the plasma membrane in SHRSP than in WKY while the Na+ pump is inactive in K+-free PSS can explain the greater relaxation observed when the Na+ pump is reactivated and 2) that the Na+ leakiness of the membrane is more attenuated by Ca2+ in the WKY than in the SHRSP. We hypothesize that this Ca2+ effect reflects a normally large amount of this ion that can be bound to and thereby stabilize the membrane of the WKY, decreasing its permeability to Na+. The membrane of the SHRSP is deficient in its Ca2+-binding sites. Hence the added Ca2+ does not further stabilize its membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1989

Increased urinary clearance of lysine vasopressin in the deoxycorticosterone acetate-hypertensive pig.

We have previously reported an increased urinary excretion of vasopressin without a rise in circulating levels of this hormone in the deoxycorticosterone acetate (DOCA)-hypertensive pig (DH). The present study was designed to characterize the renal handling of vasopressin in DH that might account for this paradox. DOCA hypertension was produced in seven domestic female pigs by means of subcutaneous implants of Silastic rubber impregnated with DOCA. Thirty days after DOCA implantation, urinary clearances of inulin, para-aminohippurate (PAH), and vasopressin were measured in the conscious animals during infusion of a 5% dextrose solution, first without and then with lysine vasopressin. Subsequent to this study, four of the pigs were placed on a low-sodium (10 meq/kg food) diet for 4 wk. At the end of this period, the clearances were again evaluated. We observed an increased urinary vasopressin clearance (CLVP) in the DH associated with an increased urinary flow but without significant changes in the clearances of inulin or PAH. Dietary sodium restrictions reversed the hypertension and the increased urinary flow and returned the CLVP to normotensive levels. These results indicate that the increased urinary excretion of vasopressin in DH is because of an increased urinary clearance of this hormone. This increased urinary CLVP is the consequence of the high urine flow in these pigs.

Animals↗
PubMed1989

Mechanical properties of carotid arteries from DOCA hypertensive swine.

Carotid arteries from control and deoxycorticosterone acetate (DOCA) hypertensive swine were examined for alterations in structure and in contractile properties. Vessels were excised 7 weeks after subcutaneous implantation of the steroid and subsequent elevation in mean arterial pressure from 102 to 133 mm Hg. The carotid media was 1.8 times thicker in arteries from hypertensive animals than in arteries from control animals. This enlargement was associated with an increase in muscle mass, as the fraction of the media composed of smooth muscle cells remained unchanged. Maximal active stress induced by several agonists normalized for cell cross-sectional area was unaltered. No change was observed in sensitivity or maximal response to norepinephrine, histamine, or KCl depolarization. Isotonic shortening rates were also comparable, as was the time course of shortening velocity to a constant afterload during tonic contractions. It is concluded that an enlargement of the carotid media develops in this model of hypertension. However, this response is not associated with detectable alterations in contractile system function.

Animals↗
PubMed1989

Dietary calcium and cell membrane abnormality in genetic hypertension.

Adult stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats were maintained for 10 weeks on one of two diets: 1.0% calcium content and 2.5% calcium content. At the end of this time rats were anesthetized, and blood pressure was determined by means of aortic cannulation; then the rats were exsanguinated. Lymphocytes were isolated for determination of intracellular sodium and potassium concentrations, net sodium influx, net potassium efflux, and intracellular free calcium concentration. Serum ionized calcium was also measured. The increase in calcium content of their diet had no effect on intracellular sodium and potassium concentrations in lymphocytes from WKY rats and SHRSP. In lymphocytes from WKY rats, none of the parameters was affected by the change in dietary calcium intake. In contrast, in lymphocytes from SHRSP the increase in dietary calcium from 1.0 to 2.5% led to significant decreases in net potassium efflux (13.3 +/- 2.3 vs. 19.7 +/- 1.4 mmol/kg dry wt/hr, p less than 0.05, analysis of variance), intracellular free calcium concentration (114.5 +/- 10.2 vs. 166.2 +/- 11.2 nM, p less than 0.001), and systolic blood pressure (125.3 +/- 13.6 vs. 183.3 +/- 16.6 mm Hg, p less than 0.01). Serum ionized calcium increased in SHRSP (2.40 +/- 0.04 vs. 2.16 +/- 0.03, p less than 0.01) but not in WKY rats (2.34 +/- 0.05 vs. 2.31 +/- 0.05) fed the high calcium diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Vascular smooth muscle in hypertension.

We have reviewed studies of the role played by abnormalities of vascular smooth muscle in hypertension. The basic contractile apparatus of this muscle appears to be qualitatively normal, but the synthetic function of the cell is exaggerated so that more contractile protein is produced. Activation pathways of the smooth muscle cell, initiated by phospholipase C, are enhanced. A reduced ability of the endothelium to produce vascular smooth muscle relaxation may contribute to an enhanced contraction of this muscle in hypertension. Furthermore, the intrinsic cellular mechanisms that produce relaxation of this muscle may also be impaired in hypertension. However, the many abnormalities observed in membrane transport systems in this muscle in hypertension suggest that the primary defect in the cell may be a lack of stability in the membrane caused by an impairment in its ability to bind calcium.

Animals↗
PubMed1988

Sodium-calcium exchange in vascular smooth muscle of Wistar-Kyoto and stroke-prone spontaneously hypertensive rats.

The role of the sodium-calcium (Na-Ca) exchange in vascular smooth muscle contraction was examined in tail artery rings isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and in normotensive Wistar-Kyoto rats (WKY). The rings were repeatedly stimulated with noradrenaline (1 microM) in physiological salt solution (Na = 130 mM), until two successive contractions were of the same magnitude. The rings were then placed in physiological salt solution with reduced sodium concentrations (65 mM or 0 mM, replaced isosmotically with sucrose), and the noradrenaline stimulations continued. In WKY rings, the reduction of sodium concentration produced an increase in the response to noradrenaline, which was significant in sodium-free physiological salt solution. In SHRSP rings, however, the same reductions in sodium concentration produced significantly less potentiation of the noradrenaline contraction, even in sodium-free physiological salt solution. We conclude that (1) in WKY, the reduced and reversed activity of the Na-Ca exchange produced by the reductions in sodium concentration makes more calcium available for contraction when the smooth muscle is stimulated with noradrenaline; and (2) the failure of sodium reductions to produce a normal potentiation of the response to noradrenaline in SHRSP indicates a depressed activity of the Na-Ca exchange in this tissue.

Animals↗