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Biomedical subjects

L L Jensen

Publications and source records attributed to L L Jensen.

15 recordsLinked to original sources
PubMed1992

Release of angiotensins in paraventricular nucleus of rat in response to physiological and chemical stimuli.

The brain angiotensin (ANG II and III) system is known to play an important role in the central control of cardiovascular function and body water homeostasis. A number of components of the angiotensin system including active peptides, precursors, synthetic enzymes, and receptors have been localized to specific brain nuclei including the paraventricular nucleus (PVN) of the hypothalamus. We and others have hypothesized that the PVN is a major integrative hub of the central angiotensin system receiving angiotensinergic input from central detectors (circumventricular organs) and sending efferents to higher brain and spinal cord centers. Implicit in this idea is that angiotensins, like all neurotransmitters, should be releasable with appropriate chemical and physiological stimuli. Therefore we examined the ability of water deprivation or direct infusion of either 65 mM K+ or 80 microM veratridine to stimulate the release of angiotensins from the PVN of the rat. Using push-pull cannulas to perfuse the PVN and radioimmunoassay (RIA) to analyze the superfusate for immunoreactive angiotensins, we established that 24 h of water deprivation resulted in an approximate 5-fold increase in the angiotensin release rate, whereas 48-h deprivation produced a dramatic 492-fold increase in release. Direct infusion of 65 mM K+ into the PVN was unable to stimulate angiotensin release, but 80 microM veratridine elicited a sevenfold increase in the angiotensin release rate. High-performance liquid chromatographic separation and RIA analysis of veratridine- and water deprivation-stimulated angiotensin release demonstrated that 93.4% of the releasable angiotensin coeluted with ANG III, whereas only 6.8% eluted with authentic ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Role of paraventricular nucleus in control of blood pressure and drinking in rats.

The present investigation examined the abilities of angiotensin (ANG) II and III to produce increases in blood pressure and drinking when microinfused into the paraventricular nucleus (PVN) of the hypothalamus of the Sprague-Dawley rat. Dose-dependent elevations in systemic blood pressure and heart rate were measured to both ANG II and III in the anesthetized rat, with ANG II more potent than ANG III at the two highest doses examined. Pretreatment with the specific ANG receptor antagonist [Sar1,Thr8]ANG II (sarthran), blocked subsequent ANG II- and III-induced elevations in blood pressure, suggesting that these responses were dependent on the activation of ANG receptors. A similar analysis in awake rats yielded nearly equivalent results. A final experiment demonstrated that microinfusions of ANG II and III into the PVN produced drinking in a dose-dependent manner, with greater consumption to ANG II than ANG III. Again, sarthran was found to block the dipsogenic response. Histological examination revealed that the location of the injection site was linked to the character of the ANG-dependent response. These data suggest that the PVN may play a critical role in mediating central ANG effects on body water homeostasis and blood pressure regulation. Furthermore, it appears that subnuclei of the PVN may participate differentially in ANG-mediated actions.

Angiotensin II↗
PubMed1990

Intracerebroventricularly applied peptidase inhibitors increase endogenous angiotensin levels.

Rats received the aminopeptidase inhibitors amastatin (AM) and bestatin (BE), and carboxypeptidase inhibitor Plummer's (PL) via intracerebroventricular infusion in various combinations, i.e. PL alone, AM + BE, and a cocktail consisting of AM + BE + PL. Blood pressure responses were recorded and a postinfusion sample of cerebrospinal fluid (CSF) was radioimmunoassayed for endogenous angiotensin levels. Results indicate that CSF angiotensin was increased approximately 1.5x over control levels when PL was infused; a 2.5x increase accompanied AM + BE administration; and a 10.3x elevation was measured when all 3 inhibitors were infused as a cocktail. Concomitant elevations in blood pressure accompanied increased concentrations of angiotensin. We conclude that endogenous levels of angiotensin can be significantly increased in the ventricular space when a combination of these inhibitors is utilized to protect both the amino and carboxyl terminals of the angiotensin molecule from enzymatic degradation.

3-Mercaptopropionic Acid↗
PubMed1990

Evaluation of an air-filled microballoon and mini-transducer in the clinical practice of anorectal manometry. Preliminary communication.

Anorectal manometry is becoming a commonly applied investigation in the field of colon and rectal surgery. Until now, however, most of this testing was performed in specialized units, which involved considerable expense and expertise to run. The authors assessed a commercially available mini-transducer and an air-filled microballoon catheter for their applicability to clinical anorectal manometry. This system is very accurate and is proving very useful in the ambulatory setting, on hospital wards, and in the operating room. It provides a simple alternative for areas where more sophisticated manometric systems are not available.

Adult↗
PubMed1990

Endorectal ultrasound in the preoperative staging of rectal tumors. A learning experience.

The preoperative staging of rectal cancer has important implications for treatment as local therapies become increasingly utilized. Seventy-seven patients underwent preoperative staging using endorectal ultrasonography. All patients had complete pathologic staging and none had preoperative radiotherapy. Depth of invasion of the tumor was accurately predicted in 75 percent of cases in the entire group, with 22 percent overstaged and 3 percent understaged. Accuracy improved greatly over the study period, and in the past six months, 95 percent have been accurately staged for depth of invasion with 5 percent overstaged. Lymph nodes have been properly classified into positive and negative groups in 88 percent of cases in the past year, with a specificity of 90 percent and a sensitivity of 88 percent. Endorectal ultrasound is an accurate preoperative staging modality. Accuracy is improved greatly with increased experience and it has been found that the 5-layer anatomical model facilitates accurate staging. Introduction of the ultrasound probe through a previously placed proctoscope ensures complete scanning of the entire lesion and should be used for the majority of examinations.

Adult↗
PubMed1989

Increased blood pressure induced by central application of aminopeptidase inhibitors is angiotensinergic-dependent in normotensive and hypertensive rat strains.

Two aminopeptidase inhibitors, amastatin (AM) and bestatin (BE), were employed in 3 strains of rats, spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD), to investigate the central angiotensinergic system. The results indicate that intracerebroventricular (i.c.v.) injections of AM and BE induced pressor elevations in all 3 strains of rats. In order to test for the possibility of spillage into peripheral vasculature, members from all 3 strains were peripherally infused with AM, BE, or 0.15 NaCl via jugular vein catheters. The SHRs were significantly more responsive to the aminopeptidases than the normotensive strains, however their overall pressor responses were only 33% of those to i.c.v. infusion. Next, in order to test the notion that these aminopeptidase inhibitors are having their effect via the central angiotensinergic system, and not some other peptidergic system, the specific angiotensin receptor antagonist, Sar1, Thr8-AII (sarthran) was employed. Intracerebroventricular pretreatment with sarthran prevented subsequent pressor responses to i.c.v. AM and BE in members of all 3 strains, thereby suggesting that these aminopeptidase inhibitors are having their effect via the central angiotensinergic system.

Aminopeptidases↗
PubMed1989

Structure-function analyses of brain angiotensin control of pressor action in rats.

The present investigation examined the relative pressor potencies of intracerebroventricularly infused angiotensin (ANG) II, successively shortened COOH-terminal fragments through ANG II(5-8), and the analogues [Sar1]ANG II through [Sar1]ANG II(5-8). The results indicate that ANG II, ANG III, [Sar1]ANG II, and [Sar1]ANG III were identical with respect to pressor responses in the alert free-moving rat. In addition, ANG II(3-8) and [Sar1]ANG II(3-8) exhibited 68-70% of the activity of the above compounds, whereas the activity of the shorter COOH-terminal fragments dropped to approximately 13-35%. Pressor responses caused by each of the active forms of angiotensin could be substantially reduced by pretreatment with the specific angiotensin receptor antagonist [Sar1,Thr8]ANG II (Sarthran), suggesting either that these ligands are acting at multiple receptors for ANG II and its fragments, which are all blocked by Sarthran, or that the ligands are acting at a common receptor site. These results, coupled with other recent findings, suggest that the brain angiotensin receptor may be designed to preferentially interact with ANG II and/or ANG III or other angiotensin analogues that structurally resemble ANG III such as [Sar1]ANG II. It is concluded that ANG III's importance as a centrally active ligand has been underestimated and that ANG III may be an active form of angiotensin in the brain.

Amino Acid Sequence↗
PubMed1989

Leucine aminopeptidase M-induced reductions in blood pressure in spontaneously hypertensive rats.

Leucine aminopeptidase M significantly reduced blood pressure for up to 40 minutes when infused intracerebroventricularly into anesthetized spontaneously hypertensive rats (SHR) from a mean +/- SEM of 190 +/- 4 to 94 +/- 7 mm Hg and also in normotensive Wistar-Kyoto (WKY) rats from 138 +/- 5 to 68 +/- 8 mm Hg. Cerebrospinal fluid levels of angiotensin II (Ang II) and III were measured by radioimmunoassay and indicated drops with leucine aminopeptidase M infusion in SHR (from 36 +/- 6 to 11 +/- 1 pg/100 microliters) and in WKY rats (from 33 +/- 9 to 13 +/- 1 pg/100 microliters). Pretreatment with the specific angiotensin receptor antagonist [Sar1, Thr8]Ang II (sarthran) significantly diminished the subsequent leucine aminopeptidase M-induced decreases in blood pressure in SHR and facilitated recovery to base level blood pressure and heart rate in blood strains. Thus, exogenous application of leucine aminopeptidase M into the brain lateral ventricles of SHR is temporarily effective at reducing blood pressure, and this effect appears dependent on the brain angiotensinergic system. This treatment also reduced blood pressure in WKY rats; however, pretreatment with sarthran was reasonably ineffective at preventing subsequent leucine aminopeptidase M-induced decreases in blood pressure.

Angiotensin II↗
PubMed1988

Central effects of a specific angiotensin receptor antagonist, sarthran (Sar1, Thr8AII) in normotensive and spontaneously hypertensive rat strains.

The specific angiotensin receptor antagonist, Sar1, Thr8AII (sarthran), was infused intracerebroventricularly in alert spontaneously hypertensive rats (SHR), and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) normotensive rat strains. This resulted in a mean decrease of 35 mm Hg in the SHR group by 25 min post-infusion, and corresponding decreases in the WKY and SD rats of 13 and 15 mm Hg, respectively. A prominent transient sarthran-induced elevation in blood pressure was noted in the SHR group during the 5-min infusion. This agonistic effect was not observed in members of the WKY and SD strains. These data encourage the use of sarthran as a valuable pharmacological probe in the examination of the role of the brain renin-angiotensin system in hypertension.

Angiotensin II↗
PubMed1988

Balloon sphincterography. Clinical findings after 200 patients.

There are two muscular mechanisms of fecal continence. The anal sphincter squeezes the anal canal, thus lengthening it and increasing its resistance. The puborectalis kinks the distal rectum, preventing the transmission of intra-abdominal pressures into the anal canal. Balloon sphincterography simultaneously records the shape of the anal canal and distal rectum and measures the strength of the puborectalis and anal sphincter muscles. This allows the physician to evaluate the function of these important muscles in patients with symptomatic defecation disorders such as constipation, incontinence, and rectal prolapse. A cylindrical balloon is connected by a hose to a fluid reservoir filled with liquid barium. The deflated balloon is placed into the anal canal and inflated by raising the fluid reservoir in increments. Fluoroscopy visualizes the balloon's shape and video records the results. Quantitative sphincterogram measurements in patients with defecation disorders include (the three measurements in each category refer respectively to incontinent patients [N = 87], prolapse patients without incontinence [N = 26], and constipated patients [N = 65]); anorectal angle (degrees + S.D.): 114 + 28, 103 + 18, 95 + 19; anal canal length (mm + S.D.): 33 + 11, 38 + 10, 39 + 10; squeeze pressure (cm H2O + S.D.): 68 + 23, 80 + 16, 91 + 22, and opening pressure (cm H2O + S.D.): 52 + 25, 67 + 22, 81 + 24. The method is useful in identifying specific defects, such as paradoxic puborectalis contractions, that can cause constipation, and injuries to the sphincters that can cause incontinence. In over 280 patients with a wide variety of defecation disorders, sphincterography has yielded information not available by standard manometric techniques. It augments the findings of defecography.

Anal Canal↗
PubMed1988

Heightened blood pressure responsiveness to intracarotid infusion of angiotensins in the spontaneously hypertensive rat.

The purpose of this study was to test the hypothesis that intracarotid infusion of angiotensin via a brachial arterial catheter results in a heightened pressor response in the alert spontaneously hypertensive rat (SHR) as previously observed for intracerebroventricular (ICV) injection of angiotensin. We infused angiotensin II and III since these ligands are equivalently potent with respect to peak pressor effect when delivered ICV. We measured somewhat greater pressor responsiveness to AII than to AIII in the Wistar-Kyoto (WKY) normotensive control strain from a baselevel of 133.1 +/- 5.8 (mean +/- SEM) to 151.3 +/- 6.2 mmHg (+13.7%) at the 100 pmol/kg/min dose of AII, and from 132.5 +/- 5.8 to 146.0 +/- 6.1 mmHg (+10.2%) for AIII. The SHR revealed a heightened pressor sensitivity to AII, from a baselevel of 170.0 +/- 3.8 to 200.6 +/- 5.9 mmHg (+18%) while the response to AIII was less dramatic, from 171.3 +/- 2.1 to 189.8 +/- 2.4 mmHg (+10.8%). These findings suggest that a similar heightened pressor responsiveness occurs to peripheral infusion of angiotensin II in the SHR as previously observed to ICV injection.

Angiotensin II↗
PubMed1987

Neurogenic heterotopic ossification.

Neurogenic heterotopic ossification is a potential sequela of neurological disorders, especially spinal cord injury and head injury. The etiology is unknown. Clinical, radiologic, and bone scan findings are typical. Complications may threaten function. The differential diagnosis is crucial in its early stages. Treatment options include diphosphonates, non-steroidal anti-inflammatory drugs, and surgery. This article has reviewed the literature on neurogenic heterotopic ossification (HO), soft tissue ossification of neurologic disease, including pathogenesis, histology, presentation, diagnosis, natural history, complications, and current treatments.

Animals↗
PubMed1986

Balloon topography. A simple method of evaluating anal function.

Balloon topography was developed to simultaneously measure anal canal pressure, anal canal length, and anorectal angle. It is performed using a cylindrical flexible balloon placed into the anal canal and rectum and filled with liquid radiopaque contrast dye under low pressure. The pressure of the dye inside the balloon is controlled by the investigator, and does not vary with changes in balloon volume. The shape of the balloon within the anal canal is recorded using fluoroscopy and plain radiopaques. The patient receives less radiation than he would receive during a single contrast barium enema. We have performed the test on 27 subjects including a normal control, rectal prolapse patients, and incontinent patients. Early results demonstrate the usefulness of the test in examining anal sphincter and pelvic floor function in maintaining fecal continence in health and disease. The test measures multiple aspects of anopelvic function simultaneously that previously required separate investigations.

Aged↗
PubMedDate not supplied

Brain angiotensin: critical role in the ongoing regulation of body fluid homeostasis and cardiovascular function.

The existence of an endogenous brain-angiotensin system and its association with cardiovascular and body water regulation has been recognized for over a decade. Nevertheless, the importance of the brain-angiotensin system to the instantaneous regulation of these processes has not been firmly established. A 5-minute intracerebroventricular (ICV) infusion of the angiotensin antagonist, [Sar1,Thr8]-AII, effectively lowered the blood pressure in normotensive rats. Additionally, application of the selective aminopeptidase inhibitor, bestatin, given alone, resulted in a dramatic increase in blood pressure and a robust drinking response. Both effects were 100% blockable by [Sar1,Thr8]-AII pretreatment. Predictably, an aminopeptidase inhibitor, bestatin, greatly elongated the half-lives of AII and AIII in the cerebroventricles. Since neither of these treatments included the introduction of exogenous angiotensins, we have concluded that perturbations of the endogenous brain-angiotensin system are effective at rapidly influencing both cardiovascular and body fluid homeostasis, thus highlighting the paramount role played by brain angiotensin in their ongoing regulation.

Aminopeptidases↗