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Biomedical subjects

D F Bohr

Publications and source records attributed to D F Bohr.

At least 73 records · Page 4Linked to original sources
PubMed1985

Mechanism by which serotonin attenuates contractile response of canine mesenteric arterial smooth muscle.

We investigated the mechanism by which prior exposure to serotonin (5-HT) attenuates contractile response to norepinephrine (NE) in dog mesenteric artery. Helically cut strips from dog mesenteric artery were mounted in muscle baths for isometric force recording. Prior treatment with 5-HT (10(-8) to 2 X 10(-7) M) attenuated the response to 2.5 X 10(-7) M NE by 26 to 61%. The attenuation lasted approximately 30 min. The attenuation is not affected by adrenergic denervation, endothelial removal, propranolol, indomethacin or arachidonate. Prior treatment with 5-HT also attenuated responses to: methoxamine, clonidine, prostaglandin F2 alpha, KCl and 5-HT itself. Inhibition of sodium influx by amiloride or inhibition of the electrogenic pump by ouabain diminished the NE attenuation. Verapamil, a calcium channel blocker, diminished the attenuation by 5-HT whereas ryanodine, an intracellular calcium release blocker, had no effect. Prior treatment with 5-HT caused a reduction in the 45Ca influx stimulated by NE. Ketanserin, a 5-HT blocker, exaggerated the attenuation of the NE response caused by 5-HT. Methysergide and cyproheptadine, also 5-HT blockers, diminished the attenuation. These results are compatible with the following interpretation: 1) 5-HT attenuates both receptor- and nonreceptor-mediated contractions of vascular smooth muscle; 2) this attenuation is the result of an increased sodium influx that stimulates the electrogenic sodium pump to cause membrane hyperpolarization and decreased stimulated calcium influx; and 3) the effects of 5-HT are mediated by 5-HT receptors that are blocked by methysergide and cyproheptadine but not by ketanserin.

Animals↗
PubMed1984

Vascular smooth muscle function and its changes in hypertension.

The contractile state of vascular smooth muscle influences arterial blood pressure and regulates organ blood flow. Current evidence suggests that the contractile apparatus of vascular smooth muscle is composed of thin and thick filaments, and that force generated between these two filaments provides the mechanism for cell shortening. The molecular events that initiate the interaction between these filaments are dependent upon the free sarcoplasmic concentration of activator calcium, which is regulated by the cell membrane and at subcellular sites. Changes in electrical activity of the cell membrane and interaction of pharmacologic agents with membrane receptors alter the cell, causing either a decrease or increase in sarcoplasmic calcium concentration and thus changing the contractile state of the vascular smooth muscle cell. Alterations in the cellular mechanisms that regulate intracellular calcium concentration may contribute to abnormal vascular function in pathologic states. In this brief review, the normal mechanism of vascular smooth muscle contraction is described, and the evidence that indicates that components of the contractile process change in hypertension is examined.

Actins↗
PubMed1984

Deoxycorticosterone acetate hypertension in the sheep.

A model of hypertension induced by mineralocoriticoid-excess in the sheep is described. Deoxycorticosterone acetate (DOCA), 100 mg/kg was implanted subcutaneously in adult sheep (n = 13). Before DOCA administration, and for 30 days thereafter, mean arterial blood pressure (MAP), plasma electrolyte levels, plasma renin activities, water and electrolyte intakes and urinary outputs were monitored. Within 72 h after DOCA implantation MAP had risen from a control value of 83.0 +/- 2.0 to 93.0 to 3.0 mmHg, MAP stabilized at 114.0 +/- 3.0 mmHg three weeks later. Water intake had increased significantly by the 4th post-implant day and reached a maximum of 10.0 +/- 1.2 l/day by the third week. The following biochemical changes were significant within 24 h after DOCA implantation; (1) plasma potassium fell from 4.4 +/- 0.1 to 3.42 +/- 0.13 mEq/l; (2) plasma sodium rose from 144.4 +/- 0.6 to 147.0 +/- 0.4 mEq/l; (3) plasma renin activity fell from 1.29 +/- 0.42 to 0.13 +/- 0.08 ng ANG l/ml/h. The rapidity of onset and reversal of arterial pressure elevation in this model render it a useful tool in providing insight into the mechanism responsible for this form of hypertension.

Animals↗
PubMed1984

Adrenergic control of coronary arteries.

This review of adrenergic control of coronary arteries is based on studies conducted on isolated vessels. Both alpha- and beta-adrenergic receptors are present in the coronary vasculature but with different distributions. The large coronary arteries have a larger percentage of alpha receptors, which mediate contraction, whereas the small coronary arteries are equipped almost exclusively with beta receptors, which mediate relaxation. The beta receptors are of the subclass beta 1. Both alpha 1 and alpha 2 receptors are present in the large coronaries. The alpha 2 receptors are prejunctional and inhibit neuronal release of norepinephrine (NE), and are also postjunctional and mediate contraction of the vascular smooth muscle. Evidence is reviewed suggesting that coronary alpha and beta receptors may be different conformational states of the same parent macromolecule in which the alpha state predominates at lower temperatures. Contrary to these results we have observed that whereas the response of the large coronary artery to NE at 39 C is predominantly constriction, it is predominantly dilation at 29 C. The characteristic of the adrenergic receptor is clearly temperature dependent.

Animals↗
PubMed1984

Aortic stiffness in the DOCA-hypertensive pig.

Pulsatile changes in aortic diameter and pressure were monitored in order to obtain an index of aortic stiffness in the conscious pig during the development of mineralocorticoid hypertension. The aortic stiffness index increased but to a much lesser extent than it did in response to a similar pressure elevation produced by phenylephrine infusion. This observation suggests that chronic exposure to an elevated pulsatile pressure reduces the stiffness index at the elevated pressure.

Animals↗
PubMed1983

Potassium-induced vascular relaxation in two kidney-one clip, renal hypertensive rats.

This study was designed to characterize potassium-induced relaxation in vascular smooth muscle in two kidney-one clip (2K-1C), renal hypertensive rats. Potassium-induced relaxation was evaluated in the isolated tail artery and in the isolated pump perfused renal vasculature. Both preparations relaxed in response to potassium after contraction induced by norepinephrine in potassium-free solution. Arterial preparations from hypertensive rats showed greater relaxation than did those from normotensive rats. Potassium-induced relaxation in tail arteries from hypertensive rats was more sensitive to ouabain inhibition than those from normotensive rats; the renal vasculature of hypertensive rats did not differ from controls with respect to ouabain sensitivity. Relaxation in response to potassium in isolated tail artery segments varied with the: 1. length of incubation in potassium-free solution; 2. concentration of added potassium; and 3. concentration of norepinephrine added during the potassium-free interval. The amplitude of potassium relaxation is believed to be a functional measure of the electrogenic sodium pump. These experiments support the hypothesis that vascular smooth muscle from 2K-1C renal hypertensive rats has increased electrogenic sodium pump activity, in vitro.

Animals↗
PubMed1983

Intrinsic difference in erythrocyte membrane in spontaneously hypertensive rats characterized by Na+ and K+ fluxes.

The goal of this study was to determine whether the elevated flux of sodium and potassium through the erythrocyte membrane of spontaneously hypertensive rats (SHR) is due to an intrinsic difference in the cell membrane or to a humoral factor present in the plasma. Isolated and washed erythrocytes from SHR and normotensive Wistar Kyoto (WKy) and Sprague-Dawley (SD) rats, were incubated in 1) a physiological salt solution, 2) WKy or SD plasma and 3) SHR plasma. Incubations were performed at 4 degrees C for 23 h. Erythrocytes from SHR incubated in physiological salt solution had significantly greater Na+ and K+ fluxes than those from normotensive WKy and SD rats (P less than 0.005). Plasma from any of the three strains of rats, as compared to physiological salt solution, increased Na+ influx in the following order: SD greater than WKy greater than SHR. Erythrocyte K+ efflux was not altered by plasma. We conclude that the elevated flux of Na+ and K+ in SHR erythrocytes is due to an intrinsic difference in the cell membrane. The greater Na+ influx in plasma from any strain of rats is not correlated with the blood pressure of the rat. The lesser increase in Na+ influx in erythrocytes incubated in plasma from SHR masks the greater intrinsic membrane permeability in the SHR erythrocyte when Na+ fluxes are studied in whole blood. The elevated flux of Na+ and K+ through the erythrocyte membrane of SHR may reflect a general membrane defect that underlies the pathogenesis of elevated arterial pressure.

Animals↗
PubMed1983

Potassium depolarization of adrenergic varicosities in resistance arteries from SHR and WKY rats.

We characterized the function of adrenergic nerve varicosities in mesenteric resistance arteries from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats by observing contractile responses to depolarization with a high potassium solution (HiK). Intact rings of resistance arteries were mounted in a specialized muscle chamber for measurement of circumferential contractile forces. Contractile responses to exogenous norepinephrine (NE), to HiK, and to the combination of NE plus HiK were significantly greater in SHR compared to WKY vessels. Using either phentolamine or 6-hydroxydopamine-treated vessels to eliminate a neurogenic adrenergic response, we determined that a part of the HiK-induced contraction was due to NE released from nerve varicosities (i.e., the adrenergic component). In order to compare these adrenergic components for possible nerve-related differences, they were first normalized to their maximum exogenous NE responses. This normalized adrenergic component of SHR vessels (52 and 58% for phentolamine and 6-hydroxydopamine treatment, respectively) was significantly greater than that of the WKY vessels (35 and 37%). This greater adrenergic component could reflect either a greater vascular smooth muscle sensitivity to NE in arteries from SHR or an increase in NE concentration, or both.

Animals↗
PubMed1983

Increased urinary vasopressin excretion in the DOCA-hypertensive pig.

A possible role for vasopressin in the development and/or maintenance of DOCA hypertension in pigs was studied. In control pigs mean arterial blood pressure (MABP), plasma lysine vasopressin (LVP) concentration, the 24-h urinary excretion of LVP (ULVPV) and plasma renin activity (PRA) did not change throughout the 30 days of the experiment. In DOCA-treated pigs MABP began to increase from the initial level of 95 +/- 2 mm Hg within 5 days and reached a level of 127 +/- 3 mm Hg between days 20-30 (P less than 0.01). At this time in the DOCA treated pigs, ULVPV increased threefold (P less than 0.05), although PLVP was unchanged and PRA was reduced to almost zero. After 30 days the pigs were fed a low sodium diet. This was without effect on MABP, PLVP and ULVPV in control pigs. However, in the DOCA-treated pigs, MABP fell from 133 +/- 2 to 112 +/- 6 mm Hg, accompanied by a 60% fall in ULVPV. PLVP was unchanged. Thus in DOCA-treated pigs, LVP appears not to be involved in the development of hypertension, but may be involved in its maintenance.

Animals↗
PubMed1983

Differential effects of DOCA on renal and gastrointestinal handling of sodium and potassium in pigs.

Young, male pigs eating standard pig chow, ad libitum, received approximately 170 mEq Na and 290 mEq K per day. Electrolyte intake, urinary and fecal electrolyte output, and plasma electrolyte levels were determined daily in 12 deoxycorticosterone acetate (DOCA)-treated pigs and in 6 control pigs. Daily Na and K balances (dietary intake - urinary + fecal output) were calculated. DOCA caused a reduction in urinary Na output from 1.53 mEq/kg/day to 0.57 mEq/kg/day during the first 48 hr following implantation. Escape from the renal sodium retaining effect of DOCA was complete within 3 days, with urinary Na output returning to pre-DOCA levels. Fecal Na output decreased from 0.65 mEq/kg/day during the preimplant period to 0.13 mEq/kg/day during the postimplant period. No escape from GI Na retention occurred by Day 15. Plasma Na rose to significantly higher levels by Day 15. Sodium balance was significantly elevated in DOCA-treated pigs for that first 48 hr postimplant. Urinary K output decreased from 3.50 mEq/kg/day to 1.74 mEq/kg/day during the first 2 days, but returned toward preimplant levels by Day 4. Fecal K output was increased for the first week, and thereafter returned to preimplant levels. Plasma K fell from 3.9 to 2.9 mEq/liter by Day 15. Potassium balance fell slightly in both experimental and control animals. No significant differences in potassium balance were present between the two groups. The control pigs showed no significant changes in plasma electrolyte concentration or in electrolyte balance. It is concluded that DOCA has differential effects on renal and gastrointestinal handling of electrolytes and that DOCA may induce an intracellular shift of potassium in pigs.

Animals↗
PubMed1982

Relaxation to transmural nerve stimulation and exogenously added norepinephrine in porcine cerebral vessels. A study utilizing cerebrovascular intrinsic tone.

The large arteries at the base of the brain in the pig were studied in vitro for their responsiveness to neurogenic and humoral stimuli. Helical strips of these cerebral vessels tonically contracted consistently following application of resting force. The development and maintenance of this tone were not influenced by prior treatment of strips with tetrodotoxin (5 x 10(-7) M), 6-hydroxydopamine (300 micrograms/ml) guanethidine (5 x 10(-6) M), or antagonists of known vasoactive autacoids (i.e., phentolamine, propranolol, atropine). Once tone reached an equilibrated plateau, transmural nerve stimulation and exogenously applied norepinephrine evoked a relaxation. The relative potency of beta-adrenergic agonists in producing a relaxation was isoproterenol greater than norepinephrine greater than epinephrine much greater than terbutaline. The response to norepinephrine, but not that to transmural nerve stimulation, was abolished by beta-adrenoceptor antagonists. The neurogenic response, but not the relaxation to exogenous catecholamines, was blocked by tetrodotoxin and 6-hydroxydopamine and diminished by guanethidine. Vasoactive intestinal polypeptide and adenosine were also potent relaxant agents. These responses, but not the response to transmural nerve stimulation were blocked by alpha-chymotrypsin (1.5 U/ml) and aminophylline (3 x 10(-5) M), respectively. These results suggest that porcine cerebral vessels develop myogenic tone which allows one to examine neural and/or humoral dilator responses without prior spasmogen addition. The vascular beta-receptors appear to be of the beta 1-subtype which is consistent with that found in other species. The nature of the dilator neurotransmitter is unknown, but the functional integrity of the adrenergic nerve terminals appears important for the neurogenic relaxation.

Animals↗
PubMed1982

Vascular smooth muscle in hypertension.

The cause of the elevated arterial pressure in most forms of hypertension is an increase in total peripheral resistance. This brief review is directed toward an assessment of recent investigations contributing information about the factors responsible for this increased vascular resistance. Structural abnormalities in the vasculature that characterize the hypertensive process are 1) changes in the vascular media, 2) rarefication of the resistance vessels, and 3) lesions of the intimal vascular surface. These abnormalities are mainly the result of an adaptive process and are secondary to the increase in wall stress and/or to pathological damage to cellular components in the vessel wall. Functional alterations in the vascular smooth muscle are described as changes in agonist-smooth muscle interaction or plasma membrane permeability. These types of changes appear to play a primary, initiating role in the elevation of vascular resistance of hypertension. These alterations are not the result of an increase in wall stress and they often precede the development of high blood pressure. The functional changes are initiated by abnormal function of neurogenic, humoral, and/or myogenic changes that alter vascular smooth muscle activity.

Angiotensin II↗
PubMed1981

Stereotaxic placement of cannulae in cerebral ventricles of the pig.

We have developed and employed a stereotaxic coordinate system for the pig brain based on eternal skull landmarks. Sagittal, coronal, and horizontal planes were defined. Based on histological maps and ventricular casts, the coordinates for locating the lateral ventricles were described. Guide tubes leading to the lateral ventricles have been chronically implanted. This access route to the ventricular system has been used for stimulation of the dipsogenic response with angiotensin and for withdrawal of cerebrospinal fluid. Solved and unsolved problems arising with these procedures have been defined.

Animals↗