Insulin resistance and coronary artery disease.
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Antihypertensive Agents↗
Biomedical subjects
D J DiPette
Publications and source records attributed to D J DiPette.
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↗
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↗
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↗
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↗
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↗
Reassessment of noradrenergic function in salt-induced hypertension in Dahl rats.
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Animals↗
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↗
Renin profile, race, and antihypertensive efficacy with atenolol and labetalol.
In this randomised double-blind parallel study, we compared the efficacy of labetalol and atenolol in a group of black (n = 33) and white (n = 34) hypertensives with uncomplicated essential hypertension after obtaining pretreatment renin profiles. After single-blind placebo (14-21 days), patients with standing diastolic BP between 105-119 mmHg were randomised to receive either labetalol (100-800 mg twice daily) or atenolol (50-100 mg once daily) to achieve a DBP less than 90 mmHg. Dosage titration occurred at weekly intervals for labetalol and biweekly for atenolol. The supine BP decrease with atenolol was -18/-14 vs. -6/-6 mmHg in whites vs. blacks respectively. With labetalol, it was -13/-12 in whites and -2/-7 mmHg in blacks. Standing BPs were: -19/-14 vs. -4/-5, whites vs. blacks with atenolol and -17/-17 vs. -19/-9 mmHg with labetalol. Neither labetalol nor atenolol was as effective in black compared with white hypertensives. The atenolol but not labetalol BP response was positively correlated with pretreatment renin values.
Atenolol↗
Digoxin-norepinephrine response and calcium blocker effects in vascular smooth muscle.
The mechanism of potentiation by digoxin of the response of vascular smooth muscle to norepinephrine was investigated in 5-cm intact segments of rabbit carotid artery. Segments were mounted in a chamber and perfused at constant pressure while flow and upstream and downstream pressures were recorded and resistance was calculated. Each vessel was perfused with a submaximal vasoconstricting concentration of norepinephrine (6 x 10(-6)M) alone, in the presence of digoxin (6 x 10(-5)M), and during exposure to both digoxin and one of the following calcium antagonists: lanthanum chloride (5 x 10(-4)M procaine hydrochloride (5 x 10(-3)M), or verapamil (5 x 10(-5)M). Digoxin potentiated the response to norepinephrine alone by 20% (P less than 0.01), to norepinephrine plus lanthanum chloride by 10% (P less than 0.001), and to norepinephrine plus procaine hydrochloride by 17% (P less than 0.001). Digoxin did not potentiate the norepinephrine response in the presence of verapamil. These data suggest that the mechanism of digoxin potentiation of the norepinephrine response in vascular smooth muscle may involve an alteration in a cellular calcium sequestration or release process. The potential cellular sites that may contribute to this phenomenon are discussed.
Animals↗
Opossum somatic sensory cortex: a microelectrode mapping study.
Organization of opossum somatic sensory cortex has been investigated utilizing closely spaced microelectrode penetrations (0.25-0.5 mm apart) and delicate mechanical stimulation of body surfaces including the facial vibrissae. Results may be summarized as follows: (1) the general organization of somatic sensory cortex, as originally defined by Lende ('63a) has been confirmed; (2) a double representation of the contralateral mystacial vibrissae and rhinarium, implicit in Lende's original data, was revealed in detail, the two representations being orderly, adjacent, mirror-images of each other; (3) units at a given cortical locus responded to deflection of between one and five mystacial vibrissae, about half responding to movement of a single vibrissa only; (4) about 40% of mystacial vibrissa units showed a directional specificity to the extent that they responded to deflections in only one or two cardinal directions; (5) units located in the medial vibrissa area showed a greater directional specificity than did units located in the lateral vibrissa area; (6) the surface area of rhinarial receptive fields was about ten times the area of first-order rhinarial unit receptive fields (B. Pubols et al., '73); (7) representation of the contralateral forelimb, especially the ventral surface of the forepaw, is extensive, orderly, and precise; (8) representation of the contralateral hindlimb, foot, and tail is minimal, and is confined to the midline convexity; (9) the presence of a small region of bilateral representation, lateral to the regions of contralateral representation, was confirmed. It is suggested that the region of contralateral postcranial representation plus the medial rhinarium and mystacial vibrissa areas are the homologue of SmI in placental mammals, and the region of bilateral representation is homologous to SmII of placental mammals, but that the lateral vibrissa and rhinarium areas are a specialization of somatic sensory cortex unique to the Virginia opossum.
Animals↗