Search PubMed⌕ Search

Biomedical subjects

D J DiPette

Publications and source records attributed to D J DiPette.

At least 37 records · Page 2Linked to original sources
PubMed1995

Mechanisms of the antihypertensive effects of dietary calcium and role of calcitonin gene related peptide in hypertension.

Alterations in calcium metabolism and calcium-regulating hormones have been described in essential hypertension. However, the mechanisms that mediate these responses are unknown. In previous studies, using the genetically spontaneously hypertensive rat and the mineralocorticoid-salt (DOC-salt) hypertensive rat model, we and others have observed that oral calcium supplementation attenuates the associated increase in peripheral vascular resistance and consequently lowers blood pressure (BP). When hypertensive patients (n = 8, diastolic BP 90-95 mmHg (1 mmHg = 133.3 Pa)) were given daily oral calcium supplementation (1.4 g elemental calcium), both systolic and diastolic BP were decreased (5-10 mmHg, p < 0.01). The only biochemical variables significantly changed were serum ionized calcium and intact parathyroid hormone (PTH, 1-84) (p < 0.05); furthermore, the levels of calcitonin gene related peptide (CGRP), measured by both radioimmunoassay and radioreceptor assay, showed a marked 75% increase (p < 0.001). The antihypertensive effects of Ca2+ and the increased levels of CGRP in the circulation returned to baseline levels immediately following cessation of calcium supplementation, suggesting that the effects of calcium on BP and CGRP are specific. On the basis of these observations were proposed that the antihypertensive effect of dietary calcium supplementation, at least in part, is mediated through CGRP.

Animals↗
PubMed1995

Enhanced neuronal expression of calcitonin gene-related peptide in mineralocorticoid-salt hypertension.

Dorsal root ganglia neuronal cell bodies synthesize the vasodilator neuropeptide calcitonin gene-related peptide and innervate the blood vessels and spinal cord sites (laminae I and II) involved in blood pressure regulation. We previously demonstrated that calcitonin gene-related peptide mRNA content is significantly decreased in dorsal root ganglia and that immunoreactive calcitonin gene-related peptide levels are reduced in laminae I and II of the dorsal horn of the spinal cord in the spontaneously hypertensive rat compared with Wistar-Kyoto control rats. To determine whether neuronal calcitonin gene-related peptide expression is also altered in mineralocorticoid-salt hypertension, we quantified calcitonin gene-related peptide mRNA levels in dorsal root ganglia and protein content in laminae I and II of the spinal cord in rats with mineralocorticoid-salt-induced hypertension. To control for pellet implantation, saline drinking water, and/or uninephrectomy, four normotensive groups were similarly studied. By Northern hybridization analysis, the ratio of calcitonin gene-related peptide mRNA to 18S rRNA was increased approximately fivefold in hypertensive rats (33 +/- 7) compared with each of the four normotensive control groups (average of the four groups, 6 +/- 0.5; P < .01, mineralocorticoid-salt group versus each group). The density of the peptide, quantified by computer-assisted image analysis, in laminae I and II in the hypertensive rats was also increased (66 +/- 1 versus average of the four groups, 46 +/- 2 arbitrary units; P < .001, mineralocorticoid-salt group versus each group). In conclusion, neuronal levels of calcitonin gene-related peptide mRNA and protein are increased in mineralocorticoid-salt hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Regulation of neuronal calcitonin gene-related peptide expression. Role of increased blood pressure.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide. We have previously demonstrated that CGRP mRNA levels are increased in dorsal root ganglia, and immunoreactive CGRP content is elevated in the spinal cord in mineralocorticoid-salt hypertension. Dorsal root ganglia neuronal cell bodies synthesize CGRP and send axons peripherally to blood vessels and centrally to spinal cord sites involved in blood pressure regulation. This increased synthesis of a potent vasodilator is a compensatory response to attenuate the increase in blood pressure; however, it is not known if neuronal CGRP is regulated simply by the elevated blood pressure or by changes in other parameters. To determine if elevation of blood pressure in normal rats induced by the administration of a potent vasoconstrictor can increase neuronal CGRP mRNA, 7-week-old male Sprague-Dawley rats were treated for 2 weeks with either angiotensin II (n = 6) or vehicle (n = 6) by using implanted osmotic minipumps. After the treatment period, the angiotensin II-treated rats displayed a marked increase in systolic blood pressure (angiotensin II, 217 +/- 18 versus control, 131 +/- 3 mm Hg, P < .001), and decrease in plasma renin activity (angiotensin II, 3.7 +/- 3.5 versus control, 35.9 +/- 14.2 ng.mL-1.h-1, P < .05). However, dorsal root ganglia CGRP mRNA content did not significantly differ between the two groups of rats. These results demonstrate that a marked increase in blood pressure, by itself, does not increase neuronal CGRP mRNA accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Hypertension induced by drugs and other substances.

The purpose of this article is to review and summarize the literature regarding the effects of medications and other substances on blood pressure. Many substances are known to cause or exacerbate hypertension, including sodium chloride, substances of abuse, nonprescription sympathomimetics, nonsteroidal anti-inflammatory drugs, sex steroids, immunosuppressive therapies, erythopoietin, antidepressants, ergot alkaloids, anesthetic agents, and other substances. With the population aging, the increasing incidence of polypharmacy, and the growth of over-the-counter pharmacological agents, including those which were previously available only by prescription, drug-induced hypertension is assuming heightened importance. Furthermore, these agents represent an important modifiable cause of secondary hypertension, and it is imperative that clinicians recognize this causal relationship.

Adrenergic Agents↗
PubMed1994

Specialty choice among students entering the fourth year of medical school.

In this article, the authors explore senior medical students' specialty preferences and investigate factors that influence those preferences. The design of the study was a written questionnaire. The setting was a large, state-supported university-based southern medical school. The patients/participants were students entering the fourth year of medical school. One hundred seventy-six students (97% of the class) completed the questionnaire. Of those students, 12.5% were interested only in primary care, 43.2% were interested in both primary and nonprimary care, and 44.3% were interested in nonprimary care careers. Most students considering both primary and nonprimary care careers were interested in general internal medicine or general pediatrics and subspecialties within those fields. Career choice was influenced most strongly by several factors--clerkship experiences, the fact that it fit with skills/abilities, physician role models, the challenge, and intellectual content. Encouragement from family and other students, prestige, and income potential had the least impact on career choice. Students interested in primary care careers valued providing continuity of care much higher than did those interested in nonprimary care specialties. The authors conclude that students' experiences in medical school, particularly during the clerkships, have a significant impact on their specialty choice.

Analysis of Variance↗
PubMed1994

Evaluating problem solving based on the use of history findings in a standardized-patient examination.

PURPOSE: To evaluate a novel item format for assessing clinical problem solving in a standardized-patient examination (SPE). METHOD: In 1992-93 a key-findings item format was included in two versions of three stations in an SPE (given in the style of an objective structured clinical examination) that was taken by 198 third-year students at the end of their three-month internal medicine clerkship at the University of Texas Medical Branch at Galveston. Each of the stations involved an extended matching question that listed ten to 12 findings. The students were told to select as many or as few findings as they wished that were key in leading them to their diagnosis of the standardized patient's (SP's) problem. The findings fell into three categories: (1) key to the diagnosis, (2) provided by the SP but not key to the diagnosis, and (3) not provided by the SP. RESULTS: A total of 169 students (85%) identified at least one of the findings determined to be key in each of the stations. Correctly identifying key findings was related to correctly diagnosing the SP's problem. A total of 145 students (73%) indicated at least one finding across the three cases as key to their diagnosis but not given by the SP. Selecting nonexistent findings as key to diagnosis was not found to be related to performance on the SPE. It was hypothesized that once a diagnosis was made, the students had difficulty differentiating key findings that had led them to the diagnosis from other key features of their cognitive model of illness. CONCLUSION: The students were generally able to obtain and recognize at least some of the key information they needed to formulate appropriate differential diagnoses, and the ability to identify key findings was shown to be related to identifying the most appropriate diagnosis. The key-findings item format has potential both in assessment and for gaining a better understanding of the clinical problem-solving process.

Clinical Competence↗
PubMed1993

The role of the renin-angiotensin system in insulin sensitivity in normotensive subjects.

Nonobese patients with essential hypertension have been reported to be insulin resistant. Because blockade of the renin-angiotensin system has been demonstrated to improve insulin sensitivity in hypertensive patients, the authors evaluated the effects of angiotensin-II administration and of angiotensin-converting enzyme inhibition with enalapril on insulin-mediated glucose uptake in normotensive men. The results showed no change in insulin sensitivity with either 0.3 ng/kg/min or 1 ng/kg/min angiotensin-II administration or with enalapril therapy. The authors conclude that neither physiologic amounts of angiotensin-II nor converting enzyme inhibition alter insulin sensitivity in normotensive men.

Adult↗
PubMed1993

Pressor doses of angiotensin II increase insulin-mediated glucose uptake in normotensive men.

The effect of pressor doses of angiotensin II infused intravenously on insulin-mediated glucose uptake was determined in normotensive men. A 3-h hyperinsulinemic euglycemic clamp was employed in 14 normotensive subjects to determine insulin-mediated glucose uptake with or without an infusion of angiotensin II (approximately 15 ng.kg-1.min-1), which increased blood pressure by 20/15 mmHg (systolic/diastolic). Addition of angiotensin II increased whole body glucose uptake by 15% (9.2 +/- 0.5 vs. 10.8 +/- 0.8 mg.kg-1 x min-1; P = 0.011), and glucose oxidation (determined by indirect calorimetry) by 25% (4.0 +/- 0.3 vs. 4.9 +/- 0.4 mg.kg-1 x min-1; P < 0.05) over insulin alone. There was no significant increase in hepatic glucose output during angiotensin II infusion (2.2 +/- 0.1 vs. 2.4 +/- 0.1 mg.kg-1 x min-1; P = NS). We conclude that angiotensin II in pressor doses increases insulin-mediated glucose disposal and oxidation. The mechanism for this may involve a redirection of blood flow into skeletal muscle during angiotensin II infusion or a direct biochemical action of angiotensin II. Although performed in lean normotensive subjects, these results cast doubt on a significant role for angiotensin II in the insulin resistance associated with essential hypertension.

Adult↗
PubMed1993

Calcitonin gene-related peptide gene expression in the spontaneously hypertensive rat.

Calcitonin gene-related peptide, a product of the calcitonin gene, is a potent vasodilator neuropeptide. We have demonstrated that dietary calcium deficiency decreased the neuronal (laminae I/II of the dorsal horn of the spinal cord) content of immunoreactive calcitonin gene-related peptide in the normal rat. Neuronal calcitonin gene-related peptide levels are also reduced in the spontaneously hypertensive rat, a model characterized by calcium deficiency. However, the mechanism of this reduction in neuronal calcitonin gene-related peptide could be due to decreased synthesis or increased release. To determine if neuronal calcitonin gene-related peptide messenger RNA (mRNA) levels are also decreased in the spontaneously hypertensive rat, we measured relative calcitonin gene-related peptide mRNA levels (using a genomic hybridization probe specific for alpha- and beta-calcitonin gene-related peptide mRNA) in dorsal root ganglia from spontaneously hypertensive and Wistar-Kyoto control rats. Dorsal root ganglia neuronal cell bodies are a prominent site of calcitonin gene-related peptide synthesis and send axons to peripheral blood vessels and central spinal cord sites (laminae I/II). After normalization of calcitonin gene-related peptide mRNA levels of 18S RNA, the calcitonin gene-related peptide mRNA/18S RNA ratio was significantly decreased approximately threefold in the spontaneously hypertensive rats compared with controls. This alteration in calcitonin gene-related peptide mRNA levels is specific for dorsal root ganglia, because no strain differences in calcitonin gene-related peptide mRNA content were detected in heart or brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Evaluation of elevated blood pressure.

The clinical laboratory is essential to the successful and complete evaluation of the patient with hypertension. A reasonably thorough knowledge of the important physiologic components of blood pressure regulation, in conjunction with a good history and physical examination and a simple panel of screening tests serve to detect or rule out the presence of secondary forms of hypertension in the majority of patients.

Adrenal Gland Diseases↗
PubMed1992

Case report: stimulation of severe hypertension as a means of malingering.

Severe hypertension frequently requires hospitalization. Although hospital admission is undesirable for most patients, others are motivated to achieve hospitalization status for secondary gain. The authors present a case of a prison inmate who simulated severe hypertension with a combination of Valsalva's maneuver and arm flexion, on the background of preexisting essential hypertension and mitral valve prolapse. His secondary intent--to avoid his prison duties--classifies him as a malingerer. The differences between this malingering and the psychiatric diagnosis of Munchausen syndrome are discussed. The contributions of essential hypertension and mitral valve prolapse to the self-induced blood pressure elevations also are considered.

Adult↗
PubMed1992

Localization and characterization of calcitonin gene-related peptide mRNA in rat heart.

Calcitonin gene-related peptide (CGRP), a product of the calcitonin/CGRP gene, is a potent vasodilating neuropeptide widely distributed throughout the cardiovascular system, particularly in the heart. Immunocytochemical studies have demonstrated CGRP-containing neurofibrils in the myocardium and in the periadventitia of coronary blood vessels. Based on these studies, it has been assumed that all of the CGRP peptide in the heart is synthesized in neurons whose cell bodies are located outside of the heart. Using Northern blot analysis and a ribonuclease protection assay, we observed in the rat heart low levels of a CGRP-like mRNA species that appeared to be identical to authentic CGRP mRNA produced in the brain and dorsal root ganglia. The ventricles contained somewhat more CGRP mRNA than did the atria. Also, whereas the dorsal root ganglia synthesized both alpha- and beta-CGRP mRNA, only the alpha-CGRP mRNA was detected in the heart. The presence of CGRP mRNA in the heart suggests that the CGRP gene is transcriptionally active in a subpopulation of heart cells, possibly neuronal, which have the potential to synthesize and secrete this neuropeptide. Given the potent coronary vasodilatory and positive chronotropic and inotropic effects of CGRP, the localized synthesis of CGRP in the heart may play a role in modulating cardiovascular function.

Animals↗
PubMed1992

Insulin enhances pressor responses to norepinephrine in rat mesenteric vasculature.

Hyperinsulinemia and insulin resistance have been proposed to play a role in human and experimental hypertension. To characterize this relation further, we examined the pressor responses to periarterial nerve stimulation (PNS) and norepinephrine infusion in the isolated mesenteric vasculature of the normal rat before and after insulin (10, 100, and 1,000 microunits/ml) infusion. The pressor responses to PNS were similar before and after insulin, except at the highest dose of insulin (1,000 microunits/ml) and the highest frequency of PNS (10 Hz). However, insulin significantly increased the pressor responses to norepinephrine. This increase in responsiveness was evident at all doses of insulin studied. In contrast, insulin did not affect the pressor responses to either angiotension II or serotonin administration. The mechanism or mechanisms for the augmented pressor response to norepinephrine after insulin infusion remain to be determined. However, the selectivity of the response for norepinephrine and the absence of a marked pressor increase after PNS indicate that the mechanism probably involves either the alpha-receptor itself or an amplification of the postreceptor signal transduction. The role of chronic hyperinsulinemia and insulin resistance in the pathogenesis of essential hypertension requires further study.

Angiotensin II↗
PubMed1992

Cardiovascular responsiveness to parathyroid hormone (PTH) and PTH-related protein in genetic hypertension.

Hypertension is often accompanied by abnormalities of calcium homeostasis, including hyperparathyroidism with reduced target organ responses to PTH in kidney and bone. Due to this association between PTH and hypertension and since PTH and the paracrine factor PTH-related protein (PTHrp) have both been shown to exert marked changes in cardiovascular activity, these actions of PTH and PTHrp were examined in spontaneously hypertensive rats (SHR) and in control normotensive Wistar-Kyoto rats (WKY). Fourteen-week-old SHR [systolic blood pressure (SBP), 201 +/- 4.4 mm Hg] and WKY (SBP, 141 +/- 2.5 mm Hg) were studied. Renal cortical membranes were prepared and assayed for radioligand binding with [125I]PTH-(1-34) and [125I]PTHrp-(1-34). There was no apparent alteration in the affinity of the binding sites to either peptide in the SHR, but specific binding in SHR renal tissue was only 60% of that observed in WKY tissue for both peptides. Serum immunoreactive PTH levels were 4-fold higher in SHR than WKY, while serum total calcium and 1,25-dihydroxyvitamin D3 levels were not different. The iv administration of both PTH and PTHrp produced dose-dependent reductions in SBP and increases in heart rate in conscious unrestrained SHR and WKY. Both peptides caused greater absolute reductions in blood pressure in SHR than in WKY. However, when the hypotensive response was normalized for the higher baseline pressure in the SHR, the blood pressure reductions caused by PTH and PTHrp were not different in SHR and WKY. Conversely, the chronotropic responses to PTH and PTHrp were lower in SHR compared to WKY. These findings indicate that the SHR exhibits elevated PTH levels, with a reduced number of renal PTH/PTHrp receptors and a depressed chronotropic response to either PTH or PTHrp. In contrast, the hypotensive response to PTH or PTHrp was not altered, indicating possible tissue-specific receptor subclasses or tissue-specific regulation of PTH and PTHrp receptors.

Animals↗
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↗