PubMed Health⌕ Search

Biomedical subjects

O B Holland

Publications and source records attributed to O B Holland.

At least 19 recordsLinked to original sources
PubMed1992

Systemic and regional hemodynamic effects of 1,25-dihydroxyvitamin D3 administration.

OBJECTIVE: To evaluate the cardiovascular effects of 1,25-dihydroxyvitamin D3 (1,25-D). DESIGN: Recent studies suggest that Ca-regulating hormones may contribute to the genesis of hypertension. We determined systemic and regional hemodynamics 24 h after administration of 1,25-D or vehicle to normal conscious Sprague-Dawley rats. In addition, to dissociate the vascular effects of 1,25-D from changes in serum ionized Ca2+, 1,25-D and vehicle were administered to rats maintained for 3 days on a low-Ca diet. To evaluate the effect of the slight rise in serum ionized Ca2+ with 1,25-D administration, we infused CaCl or vehicle over 1 h into normal rats to raise the serum Ca2+ to near that of rats treated with 1,25-D. METHODS: The radioactive microsphere technique was used. RESULTS: Systemic hemodynamics (blood pressure, heart rate, cardiac output, total peripheral resistance and stroke volume) did not differ between the two groups receiving a normal-Ca diet. In these rats 1,25-D significantly decreased renal blood flow (RBF), increased renal vascular resistance (RVR) and slightly increased serum ionized Ca2+. Similarly, in rats receiving a low-Ca diet, 1,25-D administration decreased renal blood flow, increased renal vascular resistance and caused only a minimal increase in serum ionized Ca2+. A low-Ca diet also increased heart rate, cardiac blood flow and renal blood flow. Although CaCl infusion raised serum ionized Ca2+, blood pressure, renal blood flow and renal vascular resistance did not change significantly. CONCLUSION: 1,25-D may constrict the renal vasculature directly or indirectly by enhancing the vascular sensitivity to circulating vasoconstrictors.

Animals↗
PubMed1991

Decreased spinal cord content of calcitonin gene-related peptide in the spontaneously hypertensive rat.

Calcitonin gene-related peptide (CGRP), produced by alternative processing of the primary transcript of the calcitonin gene, is a potent vasodilator. We have shown that dietary calcium deficiency accompanied by decreased serum ionized calcium significantly decreases the neuronal content of CGRP in laminae I and II of the dorsal horn of the spinal cord in the growing rat. The spontaneously hypertensive rat (SHR) is characterized by decreased serum ionized calcium levels and is thought to most closely resemble human essential hypertension. To determine if the neuronal content of CGRP is decreased in the SHR compared to the Wistar-Kyoto (WKY) parent strain, CGRP was localized immunocytochemically in the dorsal horn of the spinal cord. The density of immunocytochemical staining was quantitated by computer-assisted image processing of laminae I and II of the upper thoracic spinal cord of 12-14 week old male SHR (n = 4) and WKY (n = 4) normotensive, control rats. The SHR had significantly decreased neuronal CGRP content compared to the WKY rats (107 +/- 5 vs 121 +/- 6 arbitrary units, P less than 0.01). In contrast, the neuronal density of substance P (SP), which frequently co-exists with CGRP in this neuronal population, was not different between the two groups (SHR, 91 +/- 6 (n = 4) vs WKY, 88 +/- 3 arbitrary units (n = 4)).

Animals↗
PubMed1990

Humoral factors determining the blood pressure response to converting enzyme inhibition and calcium channel blockade.

Renin and catecholamine levels were determined in patients with mild to moderate hypertension before and after treatment with sustained release diltiazem or captopril and were correlated with the blood pressure response to these antihypertensives. Eight weeks of treatment with either agent led to equal decreases in both systolic and diastolic blood pressure. Pretreatment plasma renin activity (PRA) and plasma norepinephrine did not predict the blood pressure response to either agent. Diltiazem significantly increased both PRA and supine norepinephrine levels. However, in the diltiazem treated patients, there was no correlation between the change in plasma norepinephrine and the change in systolic or diastolic blood pressure. In contrast, there was a negative correlation (P less than .05) between the reactive rise in PRA and the decrease in systolic blood pressure. Thus, the antihypertensive response to a calcium channel blocker may be determined, in part, by the reactive response of pressor systems.

Adult↗
PubMed1990

Effects of calcium channel blockade on calcium homeostasis in mild to moderate essential hypertension.

Calcium channel blockers may alter parathyroid hormone secretion in vitro, which would alter calcium homeostasis. To determine the chronic effect of calcium channel blockade in vivo, we conducted a randomized, double blind, 16 week study comparing the effects of two pharmacologic antihypertensive agents, the calcium channel blocker diltiazem and the angiotensin-converting enzyme inhibitor captopril on parameters of calcium homeostasis. Both diltiazem and captopril lowered blood pressure to a similar degree. Neither drug produced any significant change in blood levels of total and ionized calcium, magnesium, or phosphorus, which affect the regulation of parathyroid hormone and vitamin D. In addition, at eight or 16 weeks following initiation, neither drug altered the serum levels of parathyroid hormone (PTH) or 1,25-(OH)2-vitamin D3 (1,25-D). Chronic calcium channel blockade with diltiazem does not alter serum parameters of calcium homeostasis and, thus, should not affect bone mineralization.

Adult↗
PubMed1990

Effect of dietary calcium supplementation on blood pressure and calciotropic hormones in mineralocorticoid-salt hypertension.

In order to determine the effect of dietary calcium supplementation on blood pressure and calciotropic hormones, we studied two groups (n = 12 each) of mineralocorticoid [deoxycorticosterone (DOC)]-salt hypertensive rats, one receiving a normal-calcium diet (0.6% calcium, as calcium carbonate) and the other a high-calcium diet (2.5% calcium), over an 8-week period. Dietary calcium supplementation significantly attenuated the rise in blood pressure. Serum ionized calcium concentrations were significantly decreased from baseline levels in both groups but tended to be higher among the calcium-supplemented rats. Serum concentrations of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25-D) were significantly higher in the DOC-salt rats than in normotensive rats fed normal rat chow [PTH: 49 +/- 4 versus 15 +/- 0.9 pg/ml (means +/- s.e.m.); 1,25-D: 108 +/- 7 versus 73 +/- 13 pg/ml, in DOC-salt and normotensive rats, respectively]. In the DOC-salt rats, dietary calcium supplementation did not significantly lower the elevated serum concentration of PTH (from 49 +/- 4 to 40 +/- 4 pg/ml; NS), but did significantly reduce that of 1,25-D (from 108 +/- 7 to 66 +/- 8 pg/ml; P less than 0.01). Since 1,25-D may increase vascular smooth muscle calcium uptake, dietary calcium supplementation may lower blood pressure in DOC-salt hypertension, in part, by suppressing 1,25-D.

Animals↗
PubMed1990

Importance of blood glucose concentration in regulating lipolysis during fasting in humans.

The importance of the decline in blood glucose concentration on lipolysis and the lipolytic effect of epinephrine was evaluated during short-term fasting. Lipolytic rates were determined by infusing [2H5]glycerol and [1-13C]palmitic acid. Five volunteers were studied after 12 h of fasting before and during epinephrine infusion and after 84 h of fasting, before and during glucose infusion when plasma glucose was restored to postabsorptive values, and during glucose plus epinephrine infusion. In another protocol, five volunteers were given glucose intravenously throughout fasting to maintain plasma glucose at postabsorptive levels and isotopic studies were performed after 12 and 84 h of fasting before and during epinephrine infusion. Glucose infusion after 84 h of fasting restored glucose and insulin concentrations and lipolytic rates toward 12-h fasting values. When euglycemia was maintained throughout fasting, plasma insulin still declined (P less than 0.05) and lipolytic rates still increased (P less than 0.05). Despite similar glucose concentrations, the lipolytic response to epinephrine infusion was greater after 84 h than after 12 h of fasting in both protocols (P less than 0.05). These studies demonstrate that the decline in plasma glucose contributes to, but is not required for, the increase in lipolysis during fasting. The increase in epinephrine-stimulated lipolysis that occurs during fasting is not dependent on a decrease in plasma glucose concentration.

Adult↗
PubMed1990

Combination of converting enzyme inhibitor with diuretic for the treatment of hypertension.

In recent years there has been increased discussion about goals of antihypertensive therapy other than blood pressure reduction. The development of angiotensin-converting enzyme inhibitors has provided a class of drugs with a very low side-effect profile. However, single-drug therapy is effective in only about half of hypertensive patients. In the past, diuretics have traditionally been used as the initial or second antihypertensive. Increasingly, diuretic therapy is being avoided, and other antihypertensive combinations are being used. In controlled trials, combination converting enzyme inhibitor-diuretic therapy is effective in about 85% of patients. This synergistic combination allows the diuretic dose to be reduced so that the adverse effects and metabolic complications are minimized. At this time, the combination of converting enzyme inhibitor and diuretic provides an ideal choice in terms of efficacy, compliance, side effects, and cost.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1979

Hypertension with mineralocorticoid administration to the Long-Evans rat.

1. The Carworth Long-Evans rat has been reported to develop adrenal-regeneration hypertension but not deoxycorticosterone acetate (DOCA) hypertension. Deficiency of a hypothalamic receptor for deoxycorticosterone which mediates saline polydipsia has been postulated to underlie this resistance. Since a mineralocorticoid etiology for adrenal-regeneration hypertension has been postulated and all mineralocorticoids are thought to act on common receptors, these previous reports are difficult to reconcile. 2. To determine if an absolute or relative resistance to mineralocorticoids is present, Charles River Long-Evans and Sprague-Dawley rats were given 40 mg (107 micromol) of DOCA pellets/rat or 250 microgrms (0.65 micromol) of 2 alpha-methyl-9-alpha-fluorocortisol/day subcutaneously. 3. Saline polydipsia occurred with both steroids with both rat strains, though significantly less with the Long-Evans rats. Both types of rats became hypertensive and developed cardiac and renal enlargement with both steroids. Hypertension developed more rapidly with 2 alpha-methyl-9 alpha-fluorocortisol. 4. Thus mineralocorticoid hypertension can be produced in the Charles River Long-Evans rat, and the development of adrenal-regeneration hypertension in this rat strain is not incompatible with a mineralocorticoid etiology for adrenal-regeneration hypertension.

Adrenalectomy↗
PubMed1979

Influence of 19-nor-deoxycorticosterone on blood pressure, saline consumption, and serum electrolytes, corticosterone, and renin activity.

Young, unilaterally nephrectomized, female Sprague-Dawley rats were given daily sc injections of 19-nor-deoxycorticosterone acetate (19-nor-DOCA) in oil at a dosage of 100 micrograms/day for 21 days and twice that amount for a further 11 days. One group drank distilled water and another drank 1% NaCl solution. Comparable control groups received oil injections. Another group received DOCA at the same steroid dosage and drank saline. Both 19-nor-DOCA-treated groups rapidly became hypertensive and developed cardiac hypertrophy, as did those given DOCA and saline. Saline consumption was greater in rats receiving 19-nor-DOCA, than in those given DOCA. Rats injected with 19-nor-DOCA and given water to drink showed enhanced growth and developed thymus enlargement and displayed hypokalemia and a reduction in both serum renin activity and corticosterone concentration. Plasma sodium concentration was not affected by any form of treatment. Clearly, 19-nor-DOCA is a potent mineralocorticoid and hypertensogenic agent. Since the parent steroid is known to be present abundantly in the urine of rats with regenerating adrenal glands, although circulating amounts have not yet been ascertained in that circumstance, it may be etiologically involved in adrenal regeneration hypertension, which such rats are prone to develop.

Animals↗
PubMed1979

Antihypertensive comparison of furosemide with hydrochlorothiazide for black patients.

Furosemide and hydrochlorothiazide were compared for treatment of black patients with mild to moderate hypertension in a randomized, open-label, crossover study design. Hydrochlorothiazide produced a significantly greater fall in mean arterial (24.7 vs 16.0 mm Hg, P less than .01) and diastolic (17.3 vs 10.1 mm Hg, P less than .01) blood pressure (BP) in 16 patients. Addition of methyldopa in nine patients produced a significantly greater fall in mean arterial (38.8 vs 31.9 mm Hg, P less than .05) and diastolic (28.9 vs 23.4 mm Hg, P less than .05) BP with hydrochlorothiazide vs furosemide. Renin status was categorized before and after treatment. Patients with low and normal renin activity were equally responsive to both diuretics. Hydrochlorothiazide caused a greater reduction in plasma potassium (0.26 mEg/L). Serum parathyroid hormone was not chronically elevated with furosemide. In this study, hydrochlorothiazide was more effective than furosemide for treatment of mild to moderate hypertension in black patients; renin classification did not predict diuretic responsiveness.

Adult↗
PubMed1979

Role of renin classification for diuretic treatment of black hypertensive patients.

Previous studies in white and mixed-race hypertensive patient populations have generally found patients with low renin activity more responsive to diuretic therapy than patients with normal renin activity. Twenty-nine black patients (26 women and three men) with placebo diastolic blood pressure of 90 to 115 mm Hg were treated with spironolactone (100 to 400 mg/day) and hydrochlorothiazide (100/mg/day). Renin status was categorized by (1) the intravenous furosemide test, (2) ambulation during placebo, and (3) ambulation during spironolactone and hydrochlorothiazide treatment. Only seven patients were categorized identically with all methods. No method identified a low renin subgroup that was more responsive to either spironolactone or hydrochlorothiazide. Diastolic blood pressure fall with hydrochlorothiazide (18 mm Hg) and 400 mg/day of spironolactone (15 mm Hg) was similar. Thus, since black women with both low and normal renin activity are quite responsive to diuretics, renin classification to guide initial antihypertensive selection is not warranted.

Adult↗
PubMed1978

Experimental hypertension and other responses to 18-hydroxy-deoxycorticosterone treatment in the rat.

Young female unilaterally nephrectomized, salt-loaded, Sprague-Dawley rats were treated with 200 microgram or 1 mg 18-hydroxy-deoxycorticosterone-21-acetate (18-OH-DOCA) in oil daily, and a group of kidney-intact animals on a normal salt intake was given 2 mg/day. The hormone was not found to increase saline consumption, increase urinary potassium or kallikrein excretion, or depress serum renin activity or potassium concentration. Slight hypertension did develop at 3 weeks in salt-loaded rats on the lowest dose, but this was neither increased by higher dosage or longer treatment, nor reflected by increased heart or kidney weight. The effect of 40-mg pellet implantation of DOCA and 18-OH-DOCA was then compared in unilaterally nephrectomized, salt-loaded, female Fischer 344 rats. The former caused increased saline consumption, hypertension, hypokalemia, and heart and kidney enlargement, whereas 18-OH-DOCA did not. Thus, the hypertensogenic potency of 18-OH-DOCA is, at best, a reflection of its known, very weak, mineralocorticoid activity.

18-Hydroxydesoxycorticosterone↗
PubMed1978

Plasma aldosterone response to ACTH in primary aldosteronism and in patients with low renin hypertension.

ACTH alpha 1-24 was infused at incremental rates of 12.5-200 mIU/30 min in dexamethasone-suppressed hypertensive patients on a regular sodium diet. The plasma aldosterone response to this stimulus in 8 patients with hyperaldosteronism due to an adrenal aldenoma and 11 with adrenal hyperplasia was significantly greater at all infusion rates (P less than 0.05) when compared with the response in 6 normal subjects on a similar diet. This responsiveness to ACTH in the patients with primary hyperaldosteronism was similar to that of the normal subjects on a low sodium diet. Twelve patients with low renin and 6 patients with normal renin essential hypertension were similarly studied. There was no significant difference in the median aldosterone response between these 2 groups and the normal subjects on a normal diet, but the response was significantly lower compared with that in patients with primary hyperaldosteronism. These data show that patients with hyperaldosteronism from an adrenal adenoma or hyperplasia have a consistent and exaggerated response to ACTH. The hyper-responsiveness is not apparently shared by the majority of patients with low renin essential hypertension and does not support the concept that this group is an intermediate form of primary aldosteronism. Individual patients within this group, however, may have such a response and might be identified by this type of testing.

Adenoma↗