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D J DiPette

Publications and source records attributed to D J DiPette.

69 records · Page 4Linked to original sources

Haemodynamic response to magnesium administration in mineralocorticoid-salt and two-kidney, one clip renovascular hypertension.

Recent interest has centred on the role of divalent cations in hypertension, particularly in relation to the renin-angiotensin system. This study was undertaken to determine the hypotensive effect of magnesium administration in relation to the state of activation of the renin-angiotensin system. The mean blood pressure (MBP) and heart rate (HR) response to either the acute intravenous administration of a pharmacological dose of MgSO4 or vehicle was determined in conscious mineralocorticoid-salt (DOCA-salt, low-renin) and two-kidney, one clip renovascular, high-renin hypertensive rats. Baseline MBP was higher in the renovascular than in the DOCA-salt rats, while there was no difference in HR or serum Mg concentration between the two. Following administration of MgSO4, serum Mg increased equally in both the DOCA-salt (1.4 +/- 0.8 to 4.9 +/- 0.16 mEq/l; P less than 0.001) and in the renovascular rats (1.8 +/- 0.14 to 4.4 +/- 0.27 mEq/l; P less than 0.001). Magnesium administration significantly lowered MBP over the 1-h infusion in the DOCA-salt (167 +/- 8 to 145 +/- 5 mmHg, P less than 0.001) but not the renovascular hypertensive rats (191 +/- 5 to 183 +/- 4, NS). We conclude that the blood pressure lowering effect of Mg is related, in part, to the state of activation of the renin-angiotensin system. The mechanism of this differential effect remains to be determined.

Animals↗

Hemodynamic action of calcitonin gene-related peptide in the isolated rat heart.

The effects of calcitonin gene-related peptide (CGRP) on heart rate, coronary flow, pressure development, and time to ischemic contracture were studied in the isolated, perfused rat heart. A bolus of CGRP (2640 pmols) caused significant increases in heart rate and coronary flow; these effects were sustained for at least five minutes after injection. The increase in coronary flow was independent of heart rate, since CGRP caused an increase in coronary flow in non-beating (potassium-arrested) hearts. The dose-response of CGRP was studied using five doses (65, 218, 658, 1320 and 2640 pmols) given as bolus injections. Although the increase in heart rate was apparently dose-dependent, significant increases above baseline were observed only with the two highest doses. In contrast, coronary flow increased significantly above baseline with the injection of all but the lowest dose of CGRP. Ten minutes after injection of CGRP, all hearts were made ischemic. The time to onset of ischemic contracture was approximately 11 minutes for those hearts that received 65 pmols of CGRP; however, for those hearts receiving all other doses of CGRP, the time to onset of contracture was approximately 8 minutes. We conclude that CGRP significantly decreases the resistance of the coronary vascular bed, and that it may be an important regulator of regional blood flow in the heart.

Animals↗

Postpropranolol vasodilation in adrenalectomized glucocorticoid hypertensive rats.

Acute beta-adrenoreceptor blockade results in an enhanced blood pressure-lowering effect in glucocorticoid hypertensive rats in the absence of the adrenals. To evaluate the possible mechanism of this enhanced blood pressure-lowering effect, systemic and regional hemodynamics were determined by the radioactive microsphere technique before and after propranolol administration in bilaterally adrenalectomized (AX) and sham-operated (SH) glucocorticoid hypertensive rats. Propranolol decreased mean blood pressure (BP) and heart rate (HR) to a greater extent in the AX animals. In response to propranolol, cardiac output (CO) decreased equally in both the AX and SH animals. Regional vascular responses to propranolol were similar between the AX and SH animals, except in muscle. In muscle propranolol significantly decreased blood flow and increased resistance in the SH animals. In marked contrast, in the AX animals propranolol significantly increased blood flow and decreased vascular resistance. The results of this study show that in adrenalectomized glucocorticoid hypertensive rats, the enhanced BP lowering effect of acute beta-adrenoreceptor blockade is not mediated by changes in CO. Additionally, in glucocorticoid hypertensive rats acute beta-adrenoreceptor blockade causes selective vasodilation in skeletal muscle.

Adrenalectomy↗

Systemic and regional hemodynamic effects of calcitonin gene-related peptide.

Calcitonin gene-related peptide, a 37-amino-acid neuropeptide, has been shown to be widely distributed in periadventitial nerves throughout the cardiovascular system, particularly in association with coronary arteries. In vivo and in vitro studies have demonstrated that calcitonin gene-related peptide possesses potent vasodilator properties. Circulating calcitonin gene-related peptide is derived primarily from periadventitial nerves, though its systemic and regional hemodynamic effects are unknown. In this study, systemic and regional hemodynamics were determined by the radioactive microsphere technique prior to and following the intravenous administration of 65-pmol and 2.2-nmol doses of calcitonin gene-related peptide and vehicle to three groups of conscious, unrestrained rats. Vehicle administration did not change any systemic or regional organ hemodynamic parameter determined. In contrast, 65 pmol and 2.2 nmol of calcitonin gene-related peptide significantly decreased mean blood pressure and total peripheral resistance and increased heart rate in a dose-dependent manner, while only slightly increasing cardiac output. Both 65-pmol and 2.2-nmol doses of calcitonin gene-related peptide significantly increased blood flow (percentage of cardiac output) to the heart. There was no difference in blood flow to the heart between the two doses. In addition, the 2.2-nmol dose of calcitonin gene-related peptide significantly increased blood flow to the stomach, liver, and skin and decreased it to the brain, kidneys, and spleen. In conclusion, calcitonin gene-related peptide infusion decreases blood pressure in a dose-dependent manner primarily by peripheral vasodilation. In addition, calcitonin gene-related peptide selectively changes regional organ blood flow, particularly to cause coronary vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Systemic and regional hemodynamic effect of acute magnesium administration in the normotensive and hypertensive state.

Recent interest has focused on the role that Mg2+ may play in blood pressure (BP) regulation and in hypertension. The acute effect of intravenous Mg2+ as well as vehicle administration on systemic and regional hemodynamics was determined in both normotensive rats and in rats made hypertensive by uninephrectomy followed by deoxycorticosterone acetate and salt excess (DOCA-salt). Systemic and regional hemodynamics were determined by the radioactive microsphere method in the conscious and unrestrained rat prior to and 1 h following either Mg2+ or vehicle administration. Mg2+ administration significantly increased serum Mg2+ levels in both the normotensive and DOCA-salt hypertensive rats (1.4 +/- 0.02 to 3.5 +/- 0.04 and 1.7 +/- 0.06 to 4.9 +/- 0.4 mEq/l, respectively, both p less than 0.01). The DOCA-salt rats had a significantly greater baseline mean BP, total peripheral resistance (TPR), and heart rate (HR), when compared to the normotensive rats. In the normotensive rats, neither Mg2+ or vehicle administration had any effect on either mean BP or HR. In the DOCA-salt hypertensive rats, vehicle administration had no effect on any systemic hemodynamic parameter. However, in marked contrast, Mg2+ administration significantly decreased mean BP, HR and TPR while not changing cardiac output or index. In both the normotensive and DOCA-salt hypertensive rats vehicle administration did not result in any significant regional organ vascular resistance changes. However, in the normotensive rats, Mg2+ administration significantly decreased vascular resistance in the heart and in the DOCA-salt hypertensive rats Mg2+ administration significantly decreased vascular resistance in the heart, muscle and skin while increasing vascular resistance in the stomach. In conclusion, acute Mg2+ administration significantly decreases blood pressure by peripheral vasodilation in DOCA-salt hypertensive but not in normotensive rats. In addition, acute Mg2+ administration results in a redistribution of blood flow to the heart in both the hypertensive and normotensive state as well as also possibly to the kidney and brain in the hypertensive state. The antihypertensive effect of Mg2+ in the DOCA-salt hypertensive rats as well as the prominent coronary vasodilation seen in both the normotensive and hypertensive rats may have important clinical implications.

Animals↗

Clinical use of 24-hour ambulatory blood pressure monitoring.

Knowing a patient's continuous 24-hour blood pressure measurements can be useful to the nurse practitioner in evaluating the hypertensive patient. Recent studies have demonstrated end-organ damage to have a higher degree of correlation with 24-hour blood pressure readings than with more periodic blood pressure readings. Previously, 24-hour ambulatory blood pressure determinations were evaluated primarily in research settings. The ability to obtain these readings for diagnostic information applicable to clinical situations is becoming readily available. The historical background leading to the development of the ambulatory blood pressure monitors for clinical use is reviewed. The indications for obtaining 24-hour ambulatory pressures, interpretation of specific graphs and patient outcome are explained.

Adult↗

Effect of glucose on systemic hemodynamics and blood flow rate in normal and tumor tissues in rats.

The effect of hyperglycemia on systemic hemodynamics and blood flow rate of Walker 256 carcinoma and several normal tissues of unanesthetized, unrestrained female Sprague-Dawley rats was measured, using the radioactive microsphere technique prior to and at 30 and 60 min after glucose administration (6 g/kg body weight i.v.). Whereas the mean arterial pressure and heart rate remained unchanged following glucose injection, cardiac output (CO), cardiac index, and stroke volume decreased by approximately 25% (P less than 0.05), and the total peripheral resistance increased by more than 25% (P less than 0.05). Redistribution of blood flow, expressed as a percentage of CO, among normal tissues was traced to the brain, kidneys, spleen, and liver and away from the skin, pancreas, and stomach. Changes in percentage of CO to the jejunum, colon, peritumor muscle, hindlimb, and forelimb muscles were not significant. Reduction in blood flow in large tumors (greater than 0.6 g) was proportional to the reduction in CO, and in small tumors (less than 0.6 g) was more than the reduction in CO. These results suggest that the reduction in blood flow due to hyperglycemia in large tumors is primarily due to reduction in CO and in small tumors due to both systemic and local effect; and changes in the blood flow to normal tissues should not be disregarded when using hyperglycemia in combination with hyperthermia and/or chemotherapy for cancer treatment.

Animals↗

Enalaprilat, an intravenous angiotensin-converting enzyme inhibitor, in hypertensive crises.

The effect of enalaprilat (MK-422), a newly synthesized, intravenous, nonsulfhydryl, angiotensin-converting enzyme inhibitor, was studied in seven patients with either severe or malignant hypertension. All subjects initially received a 1 mg bolus injection of enalaprilat followed in 30 minutes by 10 mg. Five subjects received an additional 40 mg. Mean (+/- SE) pretreatment blood pressure for the group was 226 +/- 9/141 +/- 7 mm Hg. Five minutes after the 1 mg enalaprilat dose, blood pressure decreased to 211 +/- 10/131 +/- 9 mm Hg and further fell to 201 +/- 14/123 +/- 11 mm Hg at 30 minutes. The maximal reduction in blood pressure to 169 +/- 14/112 +/- 10 mm Hg occurred 30 minutes after the 10 mg dose. No further blood pressure reduction was observed in those subjects who received the additional 40 mg dose. Within the entire group, five subjects exhibited sustained blood pressure reduction. No adverse side effects or symptomatic hypotension occurred in any subject.

Adult↗

Neuroleptic malignant syndrome complicated by disseminated intravascular coagulation.

The neuroleptic malignant syndrome (NMS), clinically manifested by hyperpyrexia, mental status changes, muscular rigidity, and autonomic dysfunction, is an idiosyncratic reaction to major neuroleptic pharmacologic agents. The reported causes of morbidity and mortality include respiratory insufficiency, cardiovascular collapse, arrhythmias, and renal failure. Coagulopathy does not seem to be a prominent component of the syndrome. We observed a case of NMS in which disseminated intravascular coagulation was a prominent feature.

Adult↗

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↗

The effect of intravenous enalaprilat (MK-422) administration in patients with mild to moderate essential hypertension.

The antihypertensive effect of enalaprilat (MK-422), an intravenous (IV), nonsulfhydryl converting-enzyme inhibitor, was evaluated in a double-blind study of 14 patients with mild to moderate hypertension. The seven patients in the treatment group initially received IV enalaprilat 1.25 mg q6h for 24 hours. Thereafter, responding patients (diastolic blood pressure [BP] less than or equal to 95 mm Hg) continued receiving this dose q6h for an additional 24 hours, whereas nonresponding patients were increased to IV enalaprilat 5 mg q6h for another 24 hours. Baseline BP for enalaprilat was 161 +/- 5/107 +/- 2 mm Hg (+/- SEM), and for placebo it was 150 +/- 5/103 +/- 2 mm Hg. Within the first 60 minutes, a significant reduction in both systolic and diastolic BP was noted in the enalaprilat group (P less than .05), without significant changes occurring in the placebo group. Although there was a gradual decline in both systolic and diastolic BP throughout the 48-hour study period in the placebo group, systolic and diastolic BP reduction was greater in the enalaprilat group, reaching a maximal decrease of 133 +/- 3/87 +/- 3 mm Hg. Adverse side effects did not occur in any patient.

Adult↗

Cerebral blood volume in a rat model of ischemia by MR imaging at 4.7 T.

Perturbation of the cerebral circulation by occlusion of the vertebral arteries and a carotid artery can be visualized by using MR imaging and the intravascular contrast agent Gd-DTPA complexed to albumin. This tracer consistently reduced the T1 relaxation time in the brain and blood. The difference between hemispheres was revealed by less T1 reduction in the occluded hemisphere and by an adjustment in the display contrast of images that revealed the territory of decreased perfusion. These results were confirmed by comparing them with cerebral blood flow using radioactive microspheres and the intravascular blood volume tracer 51Cr-EDTA. This method, combined with high-resolution MR imaging, can be applied to serial noninvasive studies of cerebral blood volume in ischemia and other conditions.

Animals↗