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Biomedical subjects

J P Porter

Publications and source records attributed to J P Porter.

At least 37 records · Page 2Linked to original sources
PubMed1993

Effects of blockade of AT1 and AT2 receptors in brain on the central angiotensin II pressor response in conscious spontaneously hypertensive rats.

Intracerebroventricular (i.c.v.) administration of angiotensin II (ANG II) increases vascular resistance and arterial pressure by increasing the activity in the sympathetic nervous system (SNS-component) and secretion of vasopressin (VP-component). This study examined the role of AT1 and AT2 receptors in brain in mediating the exaggerated central cardiovascular effects of ANG II in conscious, adult (10 weeks) spontaneously hypertensive rats (SHR). Mean arterial pressure, heart rate and renal blood flow responses to intraventricular injection of ANG II (100 ng in 5 microliters) were determined 10 min after intraventricular administration of the AT1 receptor antagonist losartan alone (1.0, 2.5, 5.0, 10.0 micrograms), the AT2 receptor ligand PD 123319 alone (3.5 x [10(-6), 10(-4), 10(-2), 10(0)] micrograms), or both ligands in combination. In control rats, intraventricular administration of losartan prevented the pressor and renal vascular resistance responses to intraventricular injection of ANG II, in a dose-dependent manner (P < 0.05), while intraventricular injection of PD 123319 was ineffective. Likewise, when the SNS- and VP-components were studied individually by preventing the VP-component with a V1 receptor antagonist (i.v.) or the SNS-component with chlorisondamine (i.v.), losartan (i.c.v.) prevented both components, while PD 123319 (i.c.v.) was without affect. In addition, doses of losartan, combined with 3.5 micrograms PD 123319, were no more effective in preventing the pressor or renal vascular resistance responses than losartan, administered alone, suggesting that the VP- and SNS-components of the pressor response to ANG II (i.c.v.) are mediated primarily by AT1 receptors in brain in conscious spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Contribution of spinal N-methyl-D-aspartic acid receptors to control of sympathetic outflow by the paraventricular nucleus.

Spinal NMDA receptors contribute to control of the cardiovascular system by the ventrolateral medulla. However, little is known about the contribution of these receptors to suprabulbar regulation of hemodynamics and sympathetic outflow. Hence, the involvement of spinal NMDA receptors in regulation of the cardiovascular system by the paraventricular nucleus (PVN) of the hypothalamus was investigated. In urethane-anesthetized rats, the change in mean arterial pressure (MAP), heart rate (HR), and renal nerve activity (RNA) produced by electrical or chemical activation of the PVN was determined before and after intrathecal administration of the NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (AP5). Intrathecal AP5 decreased resting MAP, HR, and RNA, but had no effect on the increase in RNA produced by electrical or chemical stimulation of the PVN. The pressor and renal vasoconstrictor effects resulting from electrical, but not chemical, stimulation of the PVN were significantly reduced by intrathecal AP5. These data show that much of the cardiovascular control exerted by the PVN does not depend on a spinal NMDA receptor mechanism.

2-Amino-5-phosphonovalerate↗
PubMed1993

Policy development lessons from two federal initiatives: protecting human research subjects and handling misconduct in science.

The authors compare and contrast two policy development exercises--one that resulted in the publication of a common federal policy for the protection of human research subjects, and the other that is under way to develop a government-wide common policy for addressing misconduct in science. The article offers some basic lessons derived from these interagency activities and may shed some light on the issues that institutions face in developing their own policies and procedures for handling allegations of misconduct in science. These lessons include, among others: lead from a position of authority; use smaller working groups to draft text or work out differences; never underestimate the time needed to elucidate where all the participants are coming from; garner support of key players; timing is everything; and when presented with lemons, make lemonade. Although the process is not yet finished, interagency work is developing concerning misconduct in science. The different participants agree in theory that coordination is desirable, but they can be understandably concerned that they might have to relinquish some of their autonomy in setting policies for activities supported by their agencies. Although it may seem that the federal government moves slowly, often there is much going on behind the scenes, and often that work can be as important as, if not more important than, the task at hand.

Federal Government↗
PubMed1992

Monoclonal antibodies to the extracellular domain of HIV-1IIIB gp160 that neutralize infectivity, block binding to CD4, and react with diverse isolates.

Ten monoclonal antibodies prepared against a soluble, recombinant form of gp160, derived from the IIIB isolate of HIV-1, were characterized. Four of the antibodies neutralized HIV-1IIIB infectivity in vitro, three blocked the binding of recombinant gp120 to CD4, three were reactive with gp41, and one preferentially reacted with an epitope on gp120 within the gp160 precursor. All three CD4 blocking antibodies bound to distinct epitopes, with one mapping to the C1 domain, one mapping to the C4 domain, and one reactive with a conformation-dependent, discontinuous epitope. Of these, the antibody reactive with the discontinuous epitope exhibited neutralizing activity against homologous and heterologous strains of HIV-1. The binding of these monoclonal antibodies to a panel of seven recombinant gp120s prepared from diverse isolates of HIV-1 was measured, and monoclonal antibodies with broad cross reactivity were identified. The epitopes recognized by 7 of the 10 monoclonal antibodies studied were localized by their reactivity with synthetic peptides and with fragments of gp120 expressed as fusion proteins in a lambda gt-11 gp160 epitope library.

Animals↗
PubMed1992

Pressor effect of posterior hypothalamic stimulation is enhanced in pregnant rats.

In contrast to the attenuated pressor response to intravenous angiotensin II (ANG II) in rat pregnancy, the response to intracerebroventricular ANG II is not blunted. To test whether this difference was due to enhanced effects of sympathetic nervous system activation, blood pressure, heart rate, and renal and mesenteric blood flow were measured in conscious term-pregnant and age-matched virgin rats during electrical stimulation of the posterior hypothalamus and during intravenous infusion of norepinephrine (NE). The pressor responses to endogenous NE release by hypothalamic stimulation were significantly greater (P less than 0.05) in pregnant rats at 10, 15 and 20 Hz. In contrast, the pressor response to exogenous NE was significantly blunted in gravid animals. These differences were not associated with significant differences in renal or mesenteric vascular resistance changes. We conclude that the lack of an attenuated response to intracerebroventricular ANG II in the pregnant rat can be explained in part by an enhanced pressor effect of sympathetic nervous system activation.

Animals↗
PubMed1992

beta-Adrenoceptor modulation of renin response to short-term reductions in pressure in young SHR.

The increase in renin secretion in response to short-term (5 min) reductions in arterial pressure has recently been shown to be similar in young spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) animals. This was puzzling, since tonic renal nerve activity is thought to be elevated in the young SHR, and this has the potential to enhance the renin response. The purpose of the present investigation was to determine whether beta-adrenoceptor modulation of pressure-dependent renin release is diminished in the SHR. In conscious, age-matched SHR, WKY, and Sprague-Dawley rats, the effect on arterial plasma renin activity of 5-min reductions in renal perfusion pressure to 90 and 50 mmHg was determined before and during beta-adrenoceptor activation with isoproterenol or beta-adrenoceptor blockade with propranolol. Isoproterenol augmented the renin response at 50 mmHg in all three strains, with the greatest effect occurring in the Sprague-Dawley rats. The response at 90 mmHg was also enhanced in the SHR and Sprague-Dawley rats, but not the WKY rats. Propranolol had no effect in the SHR and WKY animals, but significantly reduced the renin response at 50 mmHg in the Sprague-Dawley rats. Thus, under the conditions of the present investigation (i.e., short-term reductions in pressure), tonic renal nerve activity does not affect pressure-dependent renin release through a beta-adrenergic receptor mechanism in either the SHR or WKY rats. However, under conditions of acute beta-adrenoceptor activation, the renin response is enhanced at a higher renal perfusion pressure in the SHR than in the WKY rat.

Animals↗
PubMed1992

Selective preglomerular constriction to nerve stimulation in rat hydronephrotic kidneys.

The purpose of this study was to quantitate the constrictor responses of pre- vs. postglomerular microvessels during brief increases in renal nerve activity by directly observing the intact microcirculation. To validate the use of the rat hydronephrotic kidney model for this purpose, the vascular reactivity of hydronephrotic kidneys, and normal kidneys was assessed to adrenergic and neural stimulation by quantitating whole kidney blood flow velocity changes elicited by intravenous administration of norepinephrine, electrical stimulation of the posterior hypothalamus, and direct renal nerve stimulation. Hydronephrotic and nonhydronephrotic kidneys responded comparably to norepinephrine and posterior hypothalamic stimulation; however, the hydronephrotic kidneys were less responsive than normal kidneys to direct renal nerve stimulation. In the microcirculatory experiments, stimulation of the splanchnic nerve (2-8 Hz) induced a frequency-dependent constriction of interlobular arteries and afferent arterioles. Preglomerular vessel diameters decreased by 42-53% during the 8-Hz stimulation, whereas the efferent arteriolar diameters did not significantly change. Thus, constriction of preglomerular vessels mediates, in large part, the changes in renal hemodynamics evoked by increases in renal sympathetic nerve activity.

Animals↗
PubMed1990

Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160.

The development of a vaccine to provide protective immunity to human immunodeficiency virus type 1 (HIV-1), the virus causing AIDS, would be the most practical method to control its spread. Subunit vaccines consisting of virus envelope glycoproteins, produced by recombinant DNA technology, are effective in preventing viral infections. We have now used this approach in the development of a candidate AIDS vaccine. Chimpanzees were immunized with recombinant forms of the HIV-1 glycoproteins gp120 and gp160 produced in Chinese hamster ovary cells, and then challenged with HIV-1. The control and the two animals immunized with the gp160 variant became infected within 7 weeks of challenge. The two animals immunized with the gp120 variant have shown no signs of infection after more than 6 months. These studies demonstrate that recombinant gp120, formulated in an adjuvant approved for human use, can elicit protective immunity against a homologous strain of HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Effect of stress on the control of renin release in spontaneously hypertensive rats.

Recent reports suggest that centrally induced increases in sympathetic outflow to the kidney have the potential to enhance the sensitivity of pressure-dependent renin release. In the present study, the possibility was investigated that spontaneously hypertensive rats (SHR), which are thought to have increased tonic sympathetic outflow to the kidney, exhibit enhanced renin release in response to reduced renal perfusion pressure. The increase in plasma renin activity in response to a graded suprarenal aortic constriction was determined in conscious young (6-9 weeks of age) and adult (14-16 weeks of age) SHR and age-matched Wistar-Kyoto (WKY) control rats. Under conditions of relatively little stress, the renin response to reduced renal perfusion pressure was not enhanced in young or adult SHR when compared with age-matched WKY rats. That is, this regulatory mechanism was not "reset" in the hypertensive animals. When challenged with an acute stress (air to the face) both age groups of SHR exhibited a significantly enhanced response. Neither age group of WKY rats was affected by the acute air stress. These data suggest that, under unstressed conditions, pressure-dependent renin release probably does not contribute to the elevation of arterial pressure in the SHR. However, under stressful conditions, the contribution of this system may be significant. Intermittent increases in sympathetic outflow to the kidney that can occur in the SHR in response to daily stresses have the potential to render it more sensitive to spontaneous reductions in perfusion pressure. Occasional exaggerated release of renin could then contribute to the hypertensive process.

Animals↗
PubMed1989

Stress can enhance the renin response to reduced renal perfusion pressure.

It was recently reported that electrical stimulation of the hypothalamus could enhance the renin response to reductions in renal perfusion pressure. However, electrical stimulation of brain sites may activate neural pathways that never function physiologically. In the present investigation an external stress in the form of a jet of air to the face was applied to achieve a more physiological activation of the sympathetic nervous system. Conscious restrained rats, instrumented with pneumatic occluding cuffs around the aorta proximal to the renal arteries, were used to determine the relationship between renal perfusion pressure (RPP) and plasma renin activity (PRA) in the control state and in the presence of the stress. The jet of air produced a rightward shift in the relationship between RPP and PRA and also increased the slope, suggesting an enhanced sensitivity. Both the rightward shift and the increase in slope were absent in animals with bilateral renal denervation. In animals with adrenal enucleation, the rightward shift was still present but there was no significant increase in the sensitivity. These data suggest that an external activation of the central nervous system (by a stress) has the potential to modulate the responsiveness of the kidney to nonneural stimuli for renin secretion.

Adrenalectomy↗
PubMed1989

Role for central angiotensin II in control of blood pressure during pregnancy.

It is known that the pressor response to intravenous angiotensin II (ANG II) is blunted in pregnancy. In the present study we examined the pressor response to intracerebroventricular ANG II to determine whether central ANG II effects are also attenuated in conscious pregnant rats. Two to three days before experimentation, animals were instrumented with arterial and venous catheters and a ventricular guide cannula. Pressor responses to 10, 50, and 100 ng iv of ANG II, and 30, 100, and 300 ng iv of norepinephrine were significantly reduced in pregnant animals. The pressor response to 5, 20, and 50 ng iv of vasopressin was not attenuated in pregnant rats. The pressor response to intracerebroventricular 100 ng ANG II was significantly increased in pregnancy. Blockade of the vasopressin V1 receptor and the sympathetic ganglia indicated that the greater pressor response to intracerebroventricular ANG II in pregnancy may be the result of a larger contribution by the sympathetic nervous system. We conclude that the central effects of ANG II are augmented in pregnancy, suggesting a significant role for central ANG II in blood pressure regulation.

Angiotensin II↗
PubMed1989

Comparison of diagnostic tests for the detection of equine infectious anemia antibody.

Two diagnostic tests are approved for detecting antibody to equine infectious anemia virus: the agar-gel immunodiffusion (AGID) test and the competitive enzyme-linked immunosorbent assay (ELISA). A total of 420 sera from National Veterinary Services Laboratories check sets were tested with the AGID and competitive ELISA. A 100% correlation was obtained. The AGID and competitive ELISA were further used to test difficult samples with low levels of equine infectious anemia antibody (weak positives). A third test (Western blot) was also used with these weak positive samples to resolve any discordant results.

Animals↗
PubMed1988

HIV-infected cells are killed by rCD4-ricin A chain.

The gp120 envelope glycoprotein of the human immunodeficiency virus (HIV), which is expressed on the surface of many HIV-infected cells, binds to the cell surface molecule CD4. Soluble derivatives of recombinant CD4 (rCD4) that bind gp120 with high affinity are attractive vehicles for targeting a cytotoxic reagent to HIV-infected cells. Soluble rCD4 was conjugated to the active subunit of the toxin ricin. This conjugate killed HIV-infected H9 cells but was 1/1000 as toxic to uninfected H9 cells (which do not express gp120) and was not toxic to Daudi cells (which express major histocompatibility class II antigens, the putative natural ligand for cell surface CD4). Specific killing of infected cells can be blocked by rgp120, rCD4, or a monoclonal antibody to the gp120 binding site on CD4.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Vasoactive intestinal peptide and renin secretion.

VIP has now been shown to produce an increase in renin release in a number of species, including humans. Our work suggests that VIP is capable of producing this effect by a direct action on the renin-secreting juxtaglomerular cells of the kidney. We have found no evidence to support the possibility that VIP produces this effect as a neurotransmitter in the kidney. In this regard, it should be noted that VIP has been identified as a cotransmitter primarily in cholinergic neurons. The kidney is thought to lack cholinergic innervation, and acetylcholine has no effect on renin secretion. We have explored two conditions where renin secretion is known to increase and found that circulating levels of VIP did not increase along with the increase in PRA. Thus, at least in hemorrhage and dietary sodium restriction, VIP does not appear to affect renin secretion through a humoral mechanism. There could be other untested situations where a humoral effect of VIP might come into play since we have shown that the whole animal is capable of increasing plasma VIP to levels that affect renin release. Studies employing recently developed VIP antagonists have the potential to determine in which physiological or pathological situations VIP contributes to the control of renin secretion. For example, in endotoxic shock, plasma levels of both VIP and PRA are significantly elevated. Could the increase in PRA be partly dependent on an action of circulating VIP?

Animals↗
PubMed1988

Electrical stimulation of paraventricular nucleus increases plasma renin activity.

Studies employing direct electrical stimulation of the renal nerves have shown that, depending on the frequency used, selective effects on renal function can be evoked. With low frequencies, an increase in renin secretion can be elicited without affecting glomerular filtration rate, sodium excretion, or renal blood flow. In the present investigation the possibility was addressed that the central nervous system (CNS) is also organized to evoke selective changes in renal function. The paraventricular nucleus (PVN) of the hypothalamus was electrically stimulated in conscious rats with 150 microA and frequencies of 2.5, 5, 10, and 15 Hz. Blood samples for determination of plasma renin activity (PRA) were collected before and at the end of each 5-min stimulation period. The lower frequencies had no effect on PRA, but stimulation with 10 and 15 Hz produced a significant increase. This effect on PRA was not accompanied by changes in arterial pressure or renal blood flow. In a separate group of animals, stimulation of the PVN with 15 Hz produced a marked decrease in urine volume, but sodium excretion did not change. These data raise the possibility that the CNS is organized to evoke selective increases in sympathetic outflow to the kidney and to produce separate changes in renal functions.

Animals↗
PubMed1988

The renin response to aortic occlusion is enhanced by stimulation of the hypothalamus.

The sympathetic nervous system is an important factor that can induce increased renin secretion by the kidney. In recent years, the notion has arisen that the sympathetic nervous system may also function to set the level of responsiveness of the kidney to nonneural stimuli for renin secretion. However, evidence in favor of this possibility has come primarily from studies employing direct electrical stimulation of renal nerves, and no attempt has been made to determine if central neural sites can also influence the responsiveness of the kidney. In the present study, the ability of hypothalamic activation to enhance the renin response to suprarenal aortic occlusion was investigated. Conscious, freely moving rats with an inflatable cuff placed around the aorta were used to determine the relationship between renal-perfusion pressure and plasma renin activity in the control state and during continuous low-level stimulation of the paraventricular nucleus. The stimulation resulted in a rightward shift in the curve that related renal perfusion pressure to plasma renin activity; that is, for any given decrease in renal perfusion pressure, the plasma renin activity was greater during the ongoing stimulation. This rightward shift appeared to be mediated by increased renal nerve activity, since renal denervation prevented the shift. These data indicate that the hypothalamus, which plays an important role in regulating sympathetic activity, is capable of increasing the sensitivity of the kidney to a nonneural stimulus for renin secretion. This effect may become important in certain hypertensive and prehypertensive states where central neural activity is thought to be enhanced.

Animals↗
PubMed1986

A comparison of the hemodynamic effects produced by electrical stimulation of subnuclei of the paraventricular nucleus.

The paraventricular nucleus of the hypothalamus (PVN) is composed of magnocellular and parvocellular subdivisions. Magnocellular neurosecretory neurons project to the neurohypophysis while parvocellular neurons send monosynaptic axonal projections to autonomic regulatory areas in the brainstem and spinal cord. In the present study, we investigated the hemodynamic effects produced by selective magnocellular or parvocellular stimulation. In urethane anesthetized rats with intact baroreflexes, magnocellular and parvocellular stimulation produced only slight differences in hemodynamic responses, however, following acute sinoaortic denervation a clear difference was observed. Parvocellular stimulation produced an increase in arterial pressure and vasoconstriction in gut, kidney and skeletal muscle. Magnocellular stimulation produced little effect on arterial pressure and marked vasodilation in the hindquarters. Blockade of peripheral vasopressin vascular receptors did not affect the vasoconstrictor response produced by stimulation of PVN. These data are consistent with the hypothesis that the long descending neural projections of the parvocellular PVN subserve a selective vasoconstrictor function.

Animals↗