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Biomedical subjects

D F Bohr

Publications and source records attributed to D F Bohr.

At least 145 records · Page 8Linked to original sources
PubMedDate not supplied

Effects of serotonin antagonists on blood pressure in mineralocorticoid hypertensive sheep.

The serotonin antagonist methysergide has a partial agonistic action on isolated vascular smooth muscle from hypertensive animals, whereas ketanserin, another serotonin antagonist, does not. The goal of this study was to determine the effects of these two agents on blood pressure in the conscious, deoxycorticosterone acetate (DOCA) hypertensive sheep. Adult sheep maintained on a standard laboratory diet and 0.1% NaCl/0.25% KCl drinking water developed hypertension following DOCA implantation (mean arterial pressure: control = 83 mm Hg, DOCA = 108 mm Hg). Methysergide (40 micrograms/kg--i.v. bolus) produced a greater pressor response in hypertensive sheep than in normotensive sheep (control = 8 +/- 1 mm Hg, DOCA = 18 +/- 3 mm Hg). Ketanserin (50 micrograms/kg--i.v. bolus), on the other hand, caused a similar decrease in blood pressure (approximately -16 mm Hg) in both control and DOCA sheep. Pressor responses to infusions of serotonin were greater in DOCA sheep compared with controls. Both methysergide and ketanserin were equally effective antagonists of a serotonin-induced pressor response (75% inhibition) in control and DOCA sheep. Methysergide had no effect on a norepinephrine-induced pressor response, but ketanserin caused a 20% attenuation of this response. These results demonstrate an enhanced responsiveness to serotonin and methysergide in DOCA hypertensive sheep.

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Hemodynamic responses to DOCA in young pigs.

Hemodynamic variables were measured in 20 young pigs; thirteen received subcutaneous implantations of desoxycorticosterone acetate (DOCA) impregnated in Silastic strips, seven received implants of Silastic strips alone and served as controls. No salt was added to the standard diet of either group. Mean arterial pressure (MAP) rose in a regular pattern in the DOCA-treated pigs, reaching on the average a level significantly greater than that of the control group 48 hours after the implantation. Pressure continued to rise, reaching a plateau 38% above that of the preimplant value 2 weeks later. In some pigs the MAP elevation was caused by an increase in cardiac output (CO); in others it was caused by an increase in total peripheral resistance (TPR). An increase in central venous pressure occurred in many DOCA-treated pigs regardless of whether the increase in MAP was caused by an increase in CO or in TPR. The results indicate that it is arterial pressure per se that is the regulated variable in this model of mineralocorticoid hypertension. The regulating system, whether it resides in the kidney or in the central nervous system, elevates pressure by effecting increases in either CO or TPR.

Animals↗
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Electrolyte and hormonal effects of deoxycorticosterone acetate in young pigs.

Balances of sodium, potassium, and water were studied in the growing male pig as hypertension developed in response to subcutaneous implantation of deoxycorticosterone acetate (DOCA). Serum sodium, potassium, deoxycorticosterone (DOC), aldosterone, and plasma renin activity (PRA) were determined. These variables were observed in a total of 10 experimental and nine control pigs. All animals were uninephrectomized and fed a diet of Purina Pig Chow and tap water ad libitum. No salt was added to the food or water. Serum DOC levels rose dramatically on the day of the implantation, then gradually declined but remained approximately 10 times greater than control levels 40 days after implant. Plasma renin activity was suppressed rapidly and completely, whereas aldosterone fell only slowly to about half its control value. Sodium retention was maximum during the first 24 hours. Therefore an "escape" process became operative, causing sodium balance to return to normal after the third day, at which time the major rise in arterial pressure occurred. A marked increase in water turnover (intake and output) also began after the third day and persisted throughout the experimental period. Water balance remained normal during this period of increased turnover. Hypokalemia developed in the absence of kaliuresis, suggesting that potassium moved into the cells. Except for the potassium retention, these changes parallel the abnormalities seen in other states of mineralocorticoid excess.

Animals↗
PubMedDate not supplied

Nitroprusside-induced vascular relaxation in DOCA hypertensive rats.

Vascular responsiveness to nitroprusside and to norepinephrine was examined in two different preparations from DOCA hypertensive and normotensive control Sprague-Dawley rats. The blood-perfused renal vasculatures of DOCA hypertensive rats were significantly more sensitive than those of normotensive controls to the vasodilator action of low doses of nitroprusside. At high doses, responses in DOCA hypertensive and normotensive rats were similar. Since basal "structural" vascular resistances were greater in the hypertensive rats, It is possible that further vasodilation with nitroprusside was impeded more in DOCA-treated than in control rats. Nitroprusside produced a greater degree of vascular smooth muscle relaxation in tail artery strips from DOCA hypertensive rats than in those from normotensive controls. The current study is the first characterization of the effects of a vasodilator in mineralocorticoid hypertension. The two preparations gave divergent results with respect to vascular sensitivity to norepinephrine. When compared with control rats, the DOCA hypertensive rats showed a greater sensitivity to norepinephrine in tail arteries but a lesser renal vascular reactivity. It is evident that one must take a number of variables into consideration when characterizing changes in vascular responses that occur in a given model of hypertension: 1) the region of the vasculature (renal vs caudal artery);2) the level of the arterial tree (conduit vs resistance vessels);3) the technique employed for measurement of vascular changes (smooth muscle contraction vs vascular resistance changes);4) the initial vasoconstrictor tone of the preparation; and 5) the agonist used (nitroprusside vs norepinephrine).

Animals↗
PubMedDate not supplied

Vascular changes in DOCA hypertension. Influence of a low protein diet.

The goal of this study was to characterize the influence of low protein diet on vascular changes induced by deoxycorticosterone acetate (DOCA) hypertension. DOCA hypertensive and control normotensive rats were placed on a low protein (5%) diet for 4 weeks. This intervention blocked the further increase in systolic blood pressure of rats treated with DOCA; systolic blood pressures of control rats were not influenced by the low protein diet. The sensitivity of isolated mesenteric arteries to norepinephrine was increased in DOCA hypertensive rats compared to that in arteries from control rats; arterial strips from rats maintained on the low protein diet were less sensitive to the catecholamine than arteries from their respective control diet group. Vascular sensitivity to calcium was identical in both normotensive and DOCA hypertensive rats, and the low protein diet had no effect on this measure of calcium activation. Calcium-induced relaxation was depressed in arteries from DOCA hypertensive rats, suggesting a decreased stabilizing influence of the cation on the excitable membrane. Arteries from rats maintained on the low protein diet showed enhanced relaxation to calcium compared to those from their respective control diet group. Membrane stores of calcium available for activation by norepinephrine were increased in arteries from DOCA hypertensive rats; the low protein diet decreased the storage capacity of these membrane sites. The total protein content of the aorta was increased in DOCA hypertensive rats and depressed to control level in DOCA rats maintained on low protein diet. No change was observed in actomyosin content nor in the actin-to-myosin ratio during the DOCA hypertension or the addition of a low protein diet. Since one action of DOCA is to increase cellular protein synthesis, the attenuation of these vascular changes in DOCA rats maintained on a protein-deficient diet is probably due to a decrease in available substrate.

Animals↗
PubMedDate not supplied

Sustained blood pressure elevation to lower body compression in pigs and dogs.

Inflatable suits were constructed for lower body compression in pigs and dogs. The suit for pigs encompassed hindquarters and part of the abdomen, and the smaller suit for dogs compressed only the hindquarters, leaving free the abdominal cavity. In conscious, diazepam-pretreated pigs, the compression lasted 30 minutes; during that period the blood pressure increased 50/38 mm Hg over the baseline. In chloralose-anesthetized dogs, the compression was extended to 3 hours; the blood pressure increase was 44/53 mm Hg. Blood pressure fell to the baseline immediately after decompression in both animals. In both species the substantial blood pressure increase was due to an increase of vascular resistance; this did not induced the expected baroreceptor-mediated bradycardia. In dogs, the blood pressure increase was accompanied by a large increase of plasma norepinephrine (from 179 to 975 pg/ml). To test whether the increase of vascular resistance reflected the mechanical compression of the vessels under the suit, animals were pretreated with trimethaphan. In pigs the trimethaphan substantially decreased the vascular resistance and the blood pressure response. This indicated that a portion of the vasoconstriction occurred in areas outside the suit. Lower body compression is a new model to cause prolonged blood pressure elevation by noninvasive and nonpharmacologic means. The mechanism of the blood pressure elevation requires further investigation.

Abdomen↗
PubMedDate not supplied

Structural and functional changes in cerebral arteries from spontaneously hypertensive rats.

Segments of basilar arteries from both spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied in vitro utilizing a microvessel apparatus. At similar levels of passive force, basilar arteries from SHR developed less force in response to depolarizing solution (130 mM K+) compared to basilar arteries from WKY. Arterial segments from the hypertensive animals required less stretch to achieve each level of passive force. Basilar arteries from SHR but not WKY typically displayed both phasic and tonic spontaneous activity which was inhibited in a reversible manner by washing the tissues in physiological salt solution without added Ca++ (EGTA, 1 mM). There was a significant shift to the left in the EC50 of serotonin and a greater maximal response to this agonist in basilar arteries from SHR compared to those from WKY (p less than 0.01). The EC50 to Ca++ (added to a depolarizing solution) was shifted to the right in the arteries from SHR compared to the normotensive controls (p less than 0.05). There was no difference between the arteries from the two groups of animals in the relaxation response produced by isoproterenol. However, contracted basilar arteries from SHR were less sensitive to the relaxant effects of elevated Ca++ than contracted basilar arteries from WKY (p less than 0.05). These results demonstrate the existence of both structural and functional difference between cerebral vessels of SHR and WKY. Our findings also demonstrate the complex nature of the changes in calcium dynamics in blood vessels from hypertensive animals.

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Adrenergic neurotransmission in tail arteries from two-kidney, one clip, renal hypertensive rats.

The goal of this study was to determine if increased vascular smooth muscle sensitivity to norepinephrine in two-kidney, one clip (2K1C) hypertensive rats is the result of a decrease in adrenergic nerve function. Vascular sensitivity to norepinephrine was measured in isolated tail artery strips from 2K1C hypertensive and normotensive rats and in various arterial stripe preparations from normotensive rats that exhibit varying degrees of adrenergic innervation. In each case, the characteristic of the vascular smooth muscle response in the vessel with the least amount of adrenergic innervation simulated the response of the vascular smooth muscle from the 2K1C hypertensive rats. Release or displacement of endogenous norepinephrine by electrical stimulation, tyramine, potassium-free solution, and potassium excess, and measurement of tissue content of norepinephrine suggest that the blood vessels of 2K1C hypertensive animals are depleted of catecholamine stores. Based on these observations it is concluded that the increased sensitivity of vascular smooth muscle to norepinephrine in 2K1C hypertensive rats is the result of a diminished adrenergic innervation. This increased sensitivity of the vasculature may be a response of the smooth muscle cells to a decrease in innervation or the consequence of vascular wall hypertrophy leading to an increased number of smooth muscle cells that are remote from their adrenergic supply.

Adrenergic Fibers↗
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Red blood cell sodium in the DOCA hypertensive pig.

The influence of deoxycorticosterone acetate (DOCA) on the sodium content of the red blood cell was determined in the pig. DOCA (100 mg/kg), impregnated in Silastic, was implanted subcutaneously (s.c.) in six male pigs; seven additional pigs received Silastic implants without the DOCA. Those receiving DOCA had an increase in mean arterial pressure (MAP) that was significant in 48 hours and reached a plateau that was 24 mm Hg greater than that of the controls after 15 days. These animals also developed hypokalemia and polydipsia over approximately the same time course. Red blood cell sodium content increased in DOCA-treated pigs 24 hours after implant (5.57 +/- 0.17 vs 5.23 +/- 0.05, mEq/liter cells). The sodium content continued to rise, reaching a plateau 28% above that of control value by the 5th postimplant day (6.37 +/- 0.40 mEq/liter cells). In vitro tests of possible mechanisms that might have caused the in vivo increase in red blood cell sodium content gave the following results: 1) Incubations of red blood cells in a physiological salt solution (PSS) containing deoxycorticosterone failed to cause an increase in cell sodium content. 2) No ouabain-like factor was demonstrated in plasma from the DOCA hypertensive pigs. 3) An elevation in bicarbonate concentration in the PSS caused an increase in red blood cell sodium content. 4) A decrease in potassium concentration in the PSS also caused an increase in red blood cell sodium content.(ABSTRACT TRUNCATED AT 250 WORDS)

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Temperature dependence and bidirectional cation fluxes in red blood cells from spontaneously hypertensive rats.

The net passive influx of Na+ and efflux of K+ (orthodirection) through the red blood cell membranes from spontaneously hypertensive rats (SHR) were observed to be significantly higher (p less than 0.05) than those of three strains of normotensive rats when the measurements were made at 4 degrees C. Similar comparative studies, carried out at 37 degrees C, in the absence or presence of ouabain, showed no difference in these fluxes through this membrane from SHR compared to those from Wistar-Kyoto (WKY) rats, one of the normotensive strains. A study was undertaken to determine the temperature at which the greater cation fluxes in SHR red blood cells occurred. The net fluxes of Na+ and K+ decreased as the temperature was reduced from 37 degrees to 15 degrees C, but a paradoxical increase in the fluxes was observed as the temperature was decreased from 15 degrees to 4 degrees C. Only with this temperature shift (15 degrees to 4 degrees C) was the increase in flux significantly greater in SHR than in WKY cells. Subsequent studies were designed to determine whether the difference in the transport systems of red blood cells of SHR and WKY could be observed in fluxes of these cations in either direction across the membrane. For "reverse direction" flux studies, red blood cells were loaded with Na+ (to 130 mEq/liter cell water) and depleted of K+ (to 30 mEq/liter cell water) by incubation with the ionophore monensin.(ABSTRACT TRUNCATED AT 250 WORDS)

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Functional evidence for increased sodium permeability in aortas from DOCA hypertensive rats.

We studied the role of increased Na+ permeability on the increased responsiveness to ouabain and to K+-free solution in aortas from DOCA hypertensive rats. Helically cut strips from DOCA hypertensive and normotensive control rats were mounted in a muscle bath for recording isometric force. In response to ouabain, aortas from DOCA hypertensive rats were significantly more sensitive and developed a greater maximal force than aortas from control rats. The rate of force development in response to K+-free solution was significantly faster in aortas from DOCA hypertensive rats as compared to those from control rats. Monensin (10(-5)M), a Na+ ionophore, increased the contractile response to ouabain and the rate of force development in response to K+-free solution in both DOCA hypertensive and control aortas. Amiloride (3 X 10(-5) M), a Na+ channel blocker, decreased the contractile response to ouabain and the rate of force development to a K+-free solution in both the DOCA hypertensive and control aortas, but the magnitude of decrease was greater in aortas from DOCA hypertensive rats. Thus, a Na+ ionophore causes the control aortas to perform like those from DOCA hypertensive rats, and a Na+ channel blocker causes aortas from DOCA hypertensive rats to perform like those from control rats. It is concluded that the difference between the two is that the smooth muscle of aortas from DOCA hypertensive rats is more permeable to Na+ than is that from control rats.

Amiloride↗