Predicting the long-term impact of rotavirus vaccination in 112 countries from 2006 to 2034: A transmission modeling analysis.

Rotavirus vaccination has been shown to reduce rotavirus burden in many countries, but the long-term magnitude of vaccine impacts is unclear, particularly in low-income countries. We use a transmission model to estimate the long-term impact of rotavirus vaccination on deaths and disability adjusted life years (DALYs) from 2006 to 2034 for 112 low- and middle-income countries. We also explore the predicted effectiveness of a one- vs two- dose series and the relative contribution of direct vs indirect effects to overall impacts. To validate the model, we compare predicted percent reductions in severe rotavirus cases with the percent reduction in rotavirus positivity among gastroenteritis hospital admissions for 10 countries with pre- and post-vaccine introduction data. We estimate that vaccination would reduce deaths from rotavirus by 49.1 % (95 % UI: 46.6-54.3 %) by 2034 under realistic coverage scenarios, compared to a scenario without vaccination. Most of this benefit is due to direct benefit to vaccinated individuals (explaining 69-97 % of the overall impact), but indirect protection also appears to enhance impacts. We find that a one-dose schedule would only be about 57 % as effective as a two-dose schedule 12 years after vaccine introduction. Our model closely reproduced observed reductions in rotavirus positivity in the first few years after vaccine introduction in select countries. Rotavirus vaccination is likely to have a substantial impact on rotavirus gastroenteritis and its mortality burden. To sustain this benefit, the complete series of doses is needed.

Morphological characteristics of urban water bodies: mechanisms of change and implications for ecosystem function.

The size, shape, and connectivity of water bodies (lakes, ponds, and wetlands) can have important effects on ecological communities and ecosystem processes, but how these characteristics are influenced by land use and land cover change over broad spatial scales is not known. Intensive alteration of water bodies during urban development, including construction, burial, drainage, and reshaping, may select for certain morphometric characteristics and influence the types of water bodies present in cities. We used a database of over one million water bodies in 100 cities across the conterminous United States to compare the size distributions, connectivity (as intersection with surface flow lines), and shape (as measured by shoreline development factor) of water bodies in different land cover classes. Water bodies in all urban land covers were dominated by lakes and ponds, while reservoirs and wetlands comprised only a small fraction of the sample. In urban land covers, as compared to surrounding undeveloped land, water body size distributions converged on moderate sizes, shapes toward less tortuous shorelines, and the number and area of water bodies that intersected surface flow lines (i.e., streams and rivers) decreased. Potential mechanisms responsible for changing the characteristics of urban water bodies include: preferential removal, physical reshaping or addition of water bodies, and selection of locations for development. The relative contributions of each mechanism likely change as cities grow. The larger size and reduced surface connectivity of urban water bodies may affect the role of internal dynamics and sensitivity to catchment processes. More broadly, these results illustrate the complex nature of urban watersheds and highlight the need to develop a conceptual framework for urban water bodies.

Long-term sodium and chloride surface water exports from the Dallas/Fort Worth region.

Sodium and chloride in surface water are typically related to urbanization and population density and can have a significant impact on drinking water sources and the subsequent salinity of aquatic ecosystems. While the majority of research has focused on the impact of deicing salts on urban surface waters in colder climates, the effect of urbanization on sodium and chloride concentrations has been found to occur in warmer climates. This study investigated long-term exports of sodium and chloride from watersheds with increasing urbanization in the humid subtropical Dallas-Fort Worth region. We compared exports to characteristics of urbanization: urban land cover, impervious surface area, and calculated contributions from wastewater discharges. Long-term data (1980-2008) were obtained from five USGS gages located in and around the cities. Exports were calculated by regression analysis between concentrations and discharge and normalized for time and the watershed area. Grab samples were collected from June 2009 to May 2010 and sodium and chloride concentrations quantified. Our results show a strong positive relationship between the mean annual sodium and chloride exports from each watershed and the percent urban land cover and impervious surface area. Long-term increases in sodium and chloride fluxes were found for the three watersheds with the highest percentage of urban land cover. The single largest contributor was wastewater effluent that was estimated to contribute approximately half of the total loads in the three urbanized watersheds. Atmospheric deposition and deicing salts accounted for small amounts of the total export for urbanized watersheds. The source of the remaining salt load is still unknown and may be a combination of non-point sources. Estimates of urban salt exports were similar to estimates from northern watersheds affected by deicing salts.

Body mass, energy intake, and water consumption of rats and humans during space flight.

Alteration of metabolism has been suggested as a major limiting factor to long-term space flight. In humans and primates, a negative energy balance has been reported. The metabolic response of rats to space flight has been suggested to result in a negative energy balance. We hypothesized that rats flown in space would maintain energy balance as indicated by maintenance of caloric intake and body mass gain. Further, the metabolism of the rat would be similar to that of laboratory-reared animals. We studied the results from 15 space flights lasting 4 to 19 d. There was no difference in average body weight (206 +/- 13.9 versus 206 +/- 14.8 g), body weight gain (5.8 +/- 0.48 versus 5.9 +/- 0.56 g/d), caloric intake (309 +/- 21.0 versus 309 +/- 20.1 kcal/kg of body mass per day), or water intake (200 +/- 8.6 versus 199 +/- 9.3 mL/kg of body mass per day) between flight and ground control animals. Compared with standard laboratory animals of similar body mass, no differences were noted. The observations suggested that the negative balance observed in humans and non-human primates may be due to other factors in the space-flight environment.

Rat growth, body composition, and renal function during 30 days increased ambient CO2 exposure.

BACKGROUND: In experiments using rodents onboard orbiting spacecraft, specimens may be exposed to an increase in ambient CO2. HYPOTHESIS: Many of the physiological changes reported in rats (and humans) for spaceflight are similar to those observed with increased CO2, raising the question whether the observed changes are due to spaceflight or more specifically, the elevated ambient CO2. METHODS: To evaluate the effects of increased CO2, at levels similar to those experienced during spaceflight, three groups of adult male rats (n = 10) were exposed to ambient CO2 concentrations of 0.3, 0.7 and 2.0% for 30 d. Control rats were exposed to atmospheric conditions (0.03% CO2) for each group. RESULTS: There were alterations in water turnover, food intake, and renal function with increased CO2. Blood pH, total CO2, and plasma concentrations of Na+, Ca2+, and corticosterone were significantly elevated at the 2.0% exposure, while plasma PO4(3-) was reduced. At the 0.3% and 0.7% CO2 exposures, many of these changes were not significant. Animals exposed to 0.3% CO2 showed a significant increase in total body Na+. Urinary Ca2+, K+, creatinine, corticosterone, and total CO2 excretion were higher at 2.0%, but only Ca2+ and CO2 excretion were significantly elevated at 0.7%, and there was no significant alteration in renal function at 0.3%. CONCLUSION: Chronic increased ambient CO2 levels, similar to those observed on the Space Shuttle and proposed for the International Space Station, elicit compensatory responses in rats which may affect interpretation of experiments designed to evaluate the effects of exposure to microgravity.

Angiotensin II receptor binding sites in the ventral portion of the bed nucleus of the stria terminalis are reduced by interruption of the medial forebrain bundle.

Many techniques have been utilized to discern the localization of angiotensin II (Ang II) receptors to specific cellular components (glia, neuronal cell bodies and nerve terminals) in the brain. In the present study, we used lesioning techniques to localize Ang II receptors to cellular components in the rat forebrain. In the first experiment, axons ascending to the hypothalamus and forebrain from neurons in the brainstem were destroyed by unilaterally cutting the medial forebrain bundle (MFB). In the second experiment, a single injection of the neurotoxin, ibotenic acid, was injected unilaterally into the ventral portion of the bed nucleus of the stria terminalis (BSTV) to destroy neuronal cell bodies, thus determining if Ang II receptors are present on neuronal cell bodies. In both experiments, the animals were sacrificed after two weeks recovery and the brains processed for in vitro receptor autoradiography using 125I-sar1,ile8 Ang II (125I-SI Ang II). Unilateral knife-cut lesions of the MFB caused a significant reduction in 125I-SI Ang II binding in the BSTV (30+/-6%) and the piriform cortex (PC; 26+/-4%) ipsilateral to the knife cut. Unilateral injection of the neurotoxin into the BSTV failed to alter 125I-SI Ang II binding in this nucleus. These experiments suggest that at least a subpopulation of Ang II receptors in the BSTV and PC are located on terminals of neurons that have their cell bodies in the brainstem and their axons in the MFB.

Effects of chronic elevated levels of CO2 on the concentration of blood cellular elements and plasma corticosterone in the male rat.

The mean CO2 concentration on the Space Shuttle is 0.3% and has reached 0.7%, for extended periods of time. Following space flight, it has been shown that both humans and animals have significant changes in red blood cell counts (RBC) and white blood cell counts (WBC). In other studies, where no difference occurred in total WBC, a significant change did occur in the distribution of WBC. WBC are affected by circulating levels of glucocorticoids, which often increase when animals or humans are exposed to adverse and/or novel stimuli (e.g. elevated CO2 levels or weightlessness). The purpose of this study was to determine if elevations in CO2 concentration produce changes in total WBC and/or their distribution.

Intravenous losartan inhibits the increase in plasma luteinizing hormone and water intake produced by intraventricular angiotensin II.

In the presence of sex hormones, intraventricular injection of angiotensin II in female rats increases luteinizing hormone (LH) secretion, and this response is blocked by intraventricular losartan. There is evidence that in doses of 3 mg/kg or more systemically administered losartan blocks brain as well as peripheral AT1 angiotensin II receptors. Therefore, we tested the effect of intravenous losartan, 1 and 10 mg/kg, on the LH response to intraventricular angiotensin II in ovariectomized rats treated with estrogen and progesterone. The larger dose of losartan abolished the LH response. It also produced a marked reduction in the drinking response to intraventricular angiotensin II. The data provide additional evidence that in larger doses, peripherally administered losartan can penetrate the brain, and support the hypothesis that in female rats, the brain renin-angiotensin system plays an excitatory role in the regulation of LH secretion.

Involvement of central corticotropin-releasing factor (CRF) in suckling-induced inhibition of luteinizing hormone secretion in lactating rats.

The lack of ovulation and the inhibition of reproductive functions observed in many species during lactation is closely related to the intensity of the suckling stimulus. However, the mechanisms by which suckling inhibits hypothalamic GnRH and pituitary LH secretion in rats are still unclear. Since we recently demonstrated that suckling is a persistent stimulus to the adrenococortical system of the rat, we tested the hypothesis that suckling-induced activation of central CRF release may mediate the associated inhibition of GnRH secretion. Lactating females were ovariectomized (OVX) on day 2 of lactation, and equipped with icv guide cannula on day 2 and indwelling jugular catheters on day 5 before testing on day 7. Lactating females were separated from their pups for 24 h prior to the suckling test with the following pretreatments: 1) icv injection with artificial CSF (aCSF) or a specific CRF antagonist, alpha-helical CRF (9-41), (25 micrograms/rat, CRF-AX) 15 min prior to pup reunion or 2) iv injection of normal sheep serum (NSS) or CRF antiserum (CRF-AB) 4 h prior to pup reunion. Plasma ACTH, LH and PRL concentrations were determined prior to and at various intervals after pup reunion. After 3 h of suckling, LH and PRL responses to a bolus injection of GnRH (10 ng/rat) were measured; a bolus injection of Angiotensin II (AII, 5 micrograms/rat) was administered after 4 h to test for ACTH responses. Non-lactating females injected with GnRH and AII were used as controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of brain angiotensin II in the regulation of Luteinizing Hormone and Prolactin secretion.

The renin-angiotensin system, both in the circulation and in the brain, is known for its role in the regulation of fluid balance and blood pressure. The brain angiotensin II (Ang II) system is also involved in the control of anterior pituitary hormone secretion, through affecting the secretion of releasing and inhibitory factors into the hypophyseal portal vessels. Ang II controls the release of LH and PRL in a manner that is modified by ovarian hormones, observed only under specific conditions, and localized to particular regions of the brain. The identification of Ang II systems in the pituitary gland and ovary, along with data showing effects of ovarian hormones on the activity of the brain Ang II system, suggests a feedback loop whereby the brain, pituitary, and gonads interact to affect reproductive function.

Estrogens regulate angiotensin-converting enzyme and angiotensin receptors in female rat anterior pituitary.

We studied the effects of the estrous cycle, ovariectomy and estrogen replacement on angiotensin-converting enzyme (ACE) (kininase II, EC 3.4.15.1) and angiotensin II (AT) receptors in the pituitary gland of the female rat. Quantitative autoradiography, with the use of consecutive pituitary sections, allowed for simultaneous determination of changes in binding and in the potential AT synthetic ability of individual pituitaries, and for a correlation between these two phenomena. In the anterior pituitary, ACE activity and binding of the ACE inhibitor [125I]-351A were not changed during the estrous cycle. Ovariectomy produced a significant increase in ACE activity and binding, and both of these parameters returned to normal after estrogen replacement. There were no changes in ACE activity or binding in the posterior pituitary during the estrous cycle or after ovariectomy or hormone replacement. AT receptors were characterized as of the AT1 type, since they were displaced by the selective AT1 antagonist DuP 753 and not by the AT2 competitor PD 123177. There were marked changes in the concentration of AT1 receptors during the estrous cycle, with highest numbers in metestrus, lower in estrus and diestrus, and lowest during proestrus. Estrogen replacement in ovariectomized rats decreased AT1 receptor number in the anterior pituitary. Our results indicate a dual effect of estrogen on anterior pituitary AT, physiologically on AT receptor expression and pharmacologically on ACE activity.

Effects of angiotensin II on LHRH release, as measured by in vivo microdialysis of the anterior pituitary gland of conscious female rats.

The present experiments assessed the effects of central administration of angiotensin II (Ang II) on mean levels of luteinizing hormone-releasing hormone (LHRH) in the extracellular fluid of the anterior pituitary gland, monitored by in vivo microdialysis. Ovariectomized rats were tested under two conditions: (1) nonhormone-treated where Ang II infusion inhibits luteinizing hormone (LH) release, and (2) ovarian hormone-treated where Ang II stimulates LH secretion. Animals were ovariectomized and chronic guide cannulae were implanted, one into the lateral cerebral ventricle for infusion of Ang II and one directed toward the anterior pituitary gland for the insertion of the microdialysis probe. Approximately 1 week later, the dialysis probe was inserted and cemented into place. The length of the dialysis probe transected the pituitary gland from its dorsal to ventral aspects. Dialysis samples were collected at 15-min intervals. Levels of LHRH were continuously monitored in nonhormone-treated animals, prior to and during intracerebroventricular (i.c.v.) infusion of Ang II. The dialysis probe was removed at the end of the experiment. One week later, the same animals were treated with estrogen and progesterone and dialysis of the anterior pituitary gland was performed 3 days later using a protocol identical to the first dialysis sampling session. A separate group of animals was tested to confirm the effects of lateral ventricle infusion of this dose of Ang II on LH release. There were no detectable values of LHRH in dialysis samples from non-hormone-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Suckling is a persistent stimulus to the adrenocortical system of the rat.

The present experiments investigated the hypothesis that lactation constitutes a chronic stress to the adrenocortical system. To determine whether the normal circadian control of the adrenocortical system or the ability to mount an adequate ACTH response to stress are modified during lactation, we compared morning and evening basal and stress-induced ACTH, corticosterone (B), and PRL secretion as well as pituitary ACTH content and thymus weight in virgins and lactating females on day 10 of lactation. We also compared the capacity of B to suppress ACTH secretion in adrenalectomized virgin or lactating females, both given various B pellet replacement doses (40-130% B) for 5 days. In addition, we investigated the influence of decreased litter size and increased caloric intake on basal circadian activity in the adrenocortical system. Finally, we measured suckling-induced activation of ACTH and B release and restoration of basal morning ACTH and B levels after pup separation. In all 10-d lactating females, basal PRL levels were elevated compared to virgins and the circadian rhythm observed in virgins (P less than 0.05) was absent in all lactating females. By contrast, diurnal variations in ACTH and B secretion (P less than 0.05 or 0.01) were observed in all females regardless of lactation and changes in caloric intake or litter size. Plasma ACTH and B were elevated during the trough of the diurnal rhythm in mothers, compared to virgins. The amplitude of the increase in ACTH between trough and peak was greater in mothers than virgins; however, the amplitude of the increase in plasma B was greater for virgins than mothers, probably because of the higher levels of corticosteroid binding globulin in the former. Diurnal rhythms in stress responsiveness and sensitivity of ACTH to B feedback were normal in mothers; however, the magnitude of their ACTH, B, and PRL response to ether stress was less in mothers than virgins. Attempts to normalize basal ACTH and B concentrations by increasing calorie consumption were unsuccessful. However, we found that suckling caused marked stimulation of ACTH and B secretion; moreover, within 24 h after pups removal, trough ACTH and B concentrations were restored to normal values.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain Angiotensin II Receptor Subtypes and the Control of Luteinizing Hormone and Prolactin Secretion in Female Rats.

The present experiments examined the role of the two recently identified angiotensin II (Ang II) receptor subtypes, AT, and AT(2) , in the central nervous system regulation of luteinizing hormone (LH) and prolactin secretion in estrogen- and progesterone-treated ovariectomized rats. In this animal model, intracerebroventricular (icv) injection of Ang II stimulates LH and inhibits prolactin release. The specific Ang II receptor subtype antagonists losartan (AT(1) ) or PD123177 (AT(2) ) were administered (icv) in various doses (10 ng to 1,000 ng) 10 min prior to icv injection of Ang II (100 ng). Control animals were pretreated with artificial cerebrospinal fluid prior to Ang II administration. Blood samples for LH and prolactin determinations were taken from conscious, freely-moving rats prior to and following injection of the antagonists and Ang II. Water intake was measured. Ang ll-induced water intake was attenuated 62% by 1,000 ng losartan; water intake was not affected by lower doses of losartan or by any dose of PD123177. Ang ll-induced stimulation of LH release was abolished by the 1,000 ng doses of losartan and PD123177 and attenuated by the 500 ng doses of both drugs. Lower doses did not affect Ang ll-induced LH secretion. Ang ll-induced inhibition of prolactin release was significantly reduced by the 1,000 ng doses of both losartan and PD123177. Lower doses of either drug did not affect the Ang II inhibition of prolactin release. Previous studies had shown that Ang II administration into the anterior hypothalamus-medial preoptic (AHPO) area stimulated LH release. This brain area contains AT(1) receptors. To investigate the potential brain site where the AT(2) receptor may influence LH release, Ang II was injected into the locus ceruleus, a brain nucleus which contains predominately the AT(2) receptor subtype. Ang II administration into the locus ceruleus was paired with an injection of artificial cerebrospinal fluid or Ang II into the AHPO area. Injection of Ang II into the AHPO area stimulated LH release. Injection into the locus ceruleus did not affect LH secretion, nor did it modify the rise in LH elicited by administration of Ang II into the AHPO area. Plasma levels of prolactin were not altered by any of these injections. Taken together, these data demonstrate that, in estrogen- and progesterone-treated female rats, icv Ang ll-induced water intake is mediated by the AT, receptor subtype, while Ang ll-induced changes in LH and prolactin secretion appear to be mediated by both the AT(2) and AT(2) receptor subtypes. The latter observations are one of the first suggesting a potential function for the AT(2) subtype in vivo, although the physiological relevance of this observation, as well as the site of action for the effects on LH and prolactin, remain to be established.

The brain renin-angiotensin system and prolactin secretion in the male rat.

The present studies investigated the role of the brain renin-angiotensin system in the regulation of PRL secretion in the male rat. Blood samples were taken from conscious rats before, during, and after administration of test substances into the third cerebral ventricle. In the first series of experiments, we determined the sensitivity of the PRL response to intracerebroventricular (icv) administration of angiotensin II (Ang II) and found that PRL levels were significantly suppressed in a dose-related manner (10-500 ng). A dose of 1 ng did not significantly affect PRL values, compared to those from vehicle-injected animals. Ang II elicited water intake at doses of 50 and 500 ng, but not at the 10- or 1-ng doses. In the second series of experiments, we investigated the role of endogenous brain Ang II in the regulation of PRL secretion under basal and stimulated conditions. The endogenous system was manipulated by icv infusion of saralasin, an Ang II receptor antagonist, or icv injection of enalaprilat, a converting enzyme inhibitor, to prevent synthesis of Ang II. Neither saralasin nor enalaprilat administration produced an increase in PRL levels under basal, nonstressed conditions. However, during immobilization stress, when PRL levels increased 3-fold during icv vehicle infusion, saralasin infusion resulted in a 7-fold rise in plasma PRL titers relative to prestress baseline values. These results demonstrate that, in male rats, the inhibitory effects of icv administration of Ang II on PRL secretion are very sensitive and are observed at doses which do not affect water intake. The endogenous brain Ang II system appears not to be involved in the maintenance of the low plasma PRL levels observed under basal, nonstressed conditions. However, the system does appear to affect the magnitude of the PRL response to immobilization stress.

Interactions between ANP and ANG II in regulating blood pressure and sympathetic outflow.

In anesthetized rats with sinoaortic denervation, intracerebroventricular (icv) injection of atrial natriuretic peptide (ANP) resulted in decreased mean arterial blood pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) (depressor effects), whereas icv angiotensin II (ANG II) produced increases in these variables (pressor effects). The depressor effects of ANP were slower in onset and longer in duration than the pressor effects of ANG II. Intracerebroventricular injection of the ANG II-receptor blocker sarthran or the ANG II-synthesis inhibitor captopril resulted in a significant reduction in MAP; HR and RSNA were not affected. Both sarthran and captopril abolished the depressor responses to icv ANP. In contrast, injection of an anti-rat ANP antibody, which blocked the depressor effects of icv ANP, did not by itself modify MAP, HR, or RSNA, nor did the antibody affect the pressor responses to icv ANG II. These data suggest that, in this animal model, the depressor effects of icv ANP are mediated by the inhibition of brain ANG II-dependent neural activity. These results also demonstrate that, in this preparation, the endogenous ANG II system actively contributes to the maintenance of basal MAP, whereas the central ANP system, at least in regions accessible to the antirat ANP antibody, plays little role in this maintenance.

Central administration of atrial peptide decreases sympathetic outflow in rats.

Previously, we reported that intravenous (iv) administration of atrial natriuretic peptide (ANP) evokes a decrease in sympathetic outflow. This effect requires an afferent input from vagal C-fibers. Here, we examined the effect of intracerebroventricular (icv) administration of ANP on sympathetic outflow, as well as the potential role of central mechanisms in mediating the sympathoinhibitory effects evoked by systemic administration of the peptide. In anesthetized rats with arterial baroreceptors intact, injection of ANP (100-500 ng) into the third ventricle did not affect renal and least-splanchnic sympathetic nerve activities, heart rate, and mean arterial pressure. After sinoaortic denervation, however, icv injection of ANP (100 ng) decreased these variables by 8 +/- 1 and 9 +/- 2% of control nerve activity, 9 +/- 3 beats/min, and 13 +/- 2 mmHg, respectively (P less than 0.05). The inhibitory sympathetic and cardiovascular effects of icv ANP were dose dependent, with responses seen after doses too small to produce systemic effects (less than 100 ng). Vagal blockade did not abolish the effects evoked by icv ANP. In addition, iv administration of ANP did not alter reflex responses to graded electrical stimulation of afferent vagal C-fibers. Furthermore, central administration of an antiserum directed against rat ANP did not alter the inhibitory sympathetic responses evoked by iv administration of the peptide. Taken together, these results indicate that centrally administered ANP, like systemic ANP, decreases sympathetic outflow, heart rate, and blood pressure; however, the central and peripheral actions of the peptide can be distinguished and appear to be independent.

In vivo studies on paracrine actions of pituitary angiotensin II in stimulating prolactin release in rats.

The present experiments were performed to test the hypothesis that, in vivo, intrapituitary angiotensin II (ANG II) mediates the effect of luteinizing hormone-releasing hormone (LHRH) on prolactin release. After intravenous administration of LHRH (100 ng/100 microliters saline), plasma levels of both luteinizing hormone (LH) and prolactin were increased in ovariectomized rats pretreated with estradiol and progesterone. Intravenous administration of saralasin or sarthran (ANG II receptor blockers) reduced or abolished, respectively, the LHRH-induced increase in prolactin without affecting the rise in LH. In other ovariectomized steroid-treated rats, saralasin did not affect the increase in LH or prolactin induced by 10 min of restraint stress. Finally, in intact female rats on the day of proestrus, neither saralasin nor sarthran affected the mid-cycle prolactin surge. Taken together, these results show that in vivo exogenous LHRH stimulates prolactin release via a paracrine action of pituitary ANG II. However, under other conditions in which both LH and prolactin (and presumably endogenous LHRH) are elevated, pituitary ANG II does not appear to be involved in the prolactin rise.