Rain, recreation and risk: Human activity and ecological disturbance create seasonal risk landscapes for the prey of an ambush predator.

Predation risk and prey responses exhibit fluctuations in space and time. Seasonal ecological disturbances can alter landscape structure and permeability to influence predator activity and efficacy, creating predictable patterns of risk for prey (seasonal risk landscapes). This may create corresponding seasonal shifts in antipredator behaviour, mediated by species ecology and trade-offs between risk and resources. Yet, how human recreation interacts with seasonal risk landscapes and antipredator behaviour remains understudied. In South Florida, we investigated the impact of a seasonal ecological disturbance, specifically flooding, which is inversely related to human activity, on interactions between Florida panthers (Puma concolor coryi) and white-tailed deer (Odocoileus virginianus). We hypothesized that human activity and ecological disturbances would interact with panther-deer ecology, resulting in the emergence of two distinct seasonal landscapes of predation risk and the corresponding antipredator responses. We conducted camera trap surveys across southwestern Florida to collect detection data on humans, panthers and deer. We analysed the influence of human site use and flooding on deer and panther detection probability, co-occurrence and diel activity during the flooded and dry seasons. Flooding led to decreased panther detections and increased deer detections, resulting in reduced deer-panther co-occurrence during the flooded season. Panthers exhibited increased nocturnality and reduced diel activity overlap with deer in areas with higher human activity. Supporting our hypothesis, panthers' avoidance of human recreation and flooding created distinct risk schedules for deer, driving their antipredator behaviour. Deer utilized flooded areas to spatially offset predation risk during the flooded season while increasing diurnal activity in response to human recreation during the dry season. We highlight the importance of understanding how competing risks and ecological disturbances influence predator and prey behaviour, leading to the generation of seasonal risk landscapes and antipredator responses. We emphasize the role of cyclical ecological disturbances in shaping dynamic predator-prey interactions. Furthermore, we highlight how human recreation may function as a 'temporal human shield,' altering seasonal risk landscapes and antipredator responses to reduce encounter rates between predators and prey.

Deer movement and resource selection during Hurricane Irma: implications for extreme climatic events and wildlife.

Extreme climatic events (ECEs) are increasing in frequency and intensity and this necessitates understanding their influence on organisms. Animal behaviour may mitigate the effects of ECEs, but field studies are rare because ECEs are infrequent and unpredictable. Hurricane Irma made landfall in southwestern Florida where we were monitoring white-tailed deer (Odocoileus virginianus seminolus) with GPS collars. We report on an opportunistic case study of behavioural responses exhibited by a large mammal during an ECE, mitigation strategies for reducing the severity of the ECE effects, and the demographic effect of the ECE based on known-fate of individual animals. Deer altered resource selection by selecting higher elevation pine and hardwood forests and avoiding marshes. Most deer left their home ranges during Hurricane Irma, and the probability of leaving was inversely related to home range area. Movement rates increased the day of the storm, and no mortality was attributed to Hurricane Irma. We suggest deer mobility and refuge habitat allowed deer to behaviourally mitigate the negative effects of the storm, and ultimately, aid in survival. Our work contributes to the small but growing body of literature linking behavioural responses exhibited during ECEs to survival, which cumulatively will provide insight for predictions of a species resilience to ECEs and improve our understanding of how behavioural traits offset the negative impacts of global climate change.

Effects of Case Western Reserve University's transverse analysis on the quality of orthodontic treatment.

INTRODUCTION: The purpose of this study was to evaluate the effect of using the transverse analysis developed at Case Western Reserve University (CWRU) in Cleveland, Ohio. The hypotheses were based on the following: (1) Does following CWRU's transverse analysis improve the orthodontic results? (2) Does following CWRU's transverse analysis minimize the active treatment duration? METHODS: A retrospective cohort research study was conducted on a randomly selected sample of 100 subjects. The sample had CWRU's analysis performed retrospectively, and the sample was divided according to whether the subjects followed what CWRU's transverse analysis would have suggested. The American Board of Orthodontics discrepancy index was used to assess the pretreatment records, and quality of the result was evaluated using the American Board of Orthodontics cast/radiograph evaluation. The Mann-Whitney test was used for the comparison. RESULTS: CWRU's transverse analysis significantly improved the total cast/radiograph evaluation scores (P = 0.041), especially the buccolingual inclination component (P = 0.001). However, it did not significantly affect treatment duration (P = 0.106). CONCLUSIONS: CWRU's transverse analysis significantly improves the orthodontic results but does not have significant effects on treatment duration.

Antleroma in a free-ranging white-tailed deer (Odocoileus virginianus).

A 2-year-old male free-ranging white-tailed deer (Odocoileus virginianus) was diagnosed with bilateral expansile tumors of antler origin. The deer was found dead by a landowner in High Springs, Florida. Two roughly spherical, multilobular, broad-based, bony, velvet-covered masses originated from each antler pedicle. These masses replaced or displaced many of the bones and soft tissues of the skull and extended through the left cribriform plate and the right petrous temporal bone, compressing portions of the brain. Microscopically, the masses closely resembled normal-growing antler, containing all the elements thereof but with areas of necrosis and hemorrhage suggestive of ischemi or trauma. Tumorlike outgrowths termed antleromas have been described in free-ranging and captive cervids and typically are associated with disruptions in the seasonal rise and fall of circulating testosterone necessary for normal antler growth, casting, and regeneration.

On the origin of siphonariid polypropionates: total synthesis of baconipyrone A, baconipyrone C, and siphonarin B via their putative common precursor.

The hypothesis that siphonariid polypropionates originate from nonenzymatic processes on acyclic biosynthetic precursors was tested by examining the properties of the putative common precursor for the S. zelandica decapropionates siphonarin B, caloundrin B, baconipyrone A, and baconipyrone C, i.e., (4S,5S,6S,8RS,10S,11S,12R,14R)-14-(6-ethyl-3,5-dimethyl-4-oxo-4H-pyran-2-yl)-5,11-dihydroxy-4,6,8,10,12-pentamethylpentadecane-3,7,9,13-tetraone. The first synthesis of such a precursor was achieved in an efficient and fully enantioselective manner using a thiopyran-based strategy for polypropionate synthesis. This putative precursor, a complex mixture of ring-chain and keto-enol tautomers, was kinetically stable and isomerized exceedingly slowly to the thermodynamically more stable siphonarin B. In the presence of imidazole, the mixture reached apparent equilibrium within several hours giving siphonarin B as the predominant component (ca. 70%), thereby constituting its enantioselective total synthesis. In the presence of alumina, both siphonarin B and the dihydroxytetraone precursor underwent retro-Claisen rearrangements (via a hemiacetal tautomer) to give baconipyrones A and C among other products. This is the first total synthesis of baconipyrone A and "biomimetic" synthesis of baconipyrone C. Control experiments suggested that baconipyrone A was produced in an unprecedented cascade process where the intermediate enol(ate) of the retro-Claisen rearrangement was directly engaged in aldol cyclization while baconipyrone C resulted from simple ketonization of the enol(ate). These experiments provide the first unambiguous demonstration that the baconipyrones are plausible isolation artifacts and suggest they are most likely derived from siphonarins rather than an "acyclic" precursor. Caloundrin B was not detected among the products from any of the isomerization experiments, suggesting the possibility that it is an unstable biosynthetic product.

Synthetic studies on siphonariid polypropionates: synthesis and isomerization of the caloundrin B trioxaadamantane ring system.

(1R,3R,5R,7R,8S,9R,10S)-3,5-Diethyl-8,9,10-trimethyl-2,4,6-trioxatricyclo[3.3.1.1(3,7)]decan-1-ol (II), a model of the trioxaadamantane ring system embedded in caloundrin B, was prepared by isomerization of the thermodynamically unstable (9S)-diastereomer (I) in the presence of imidazole. Alternatively, isomerization of I with HF.py or DBU gave the hemiacetal III or its retro-Claisen ester IV, respectively, which represent structural motifs present in the closely related siphonariid polypropionates siphonarin B and baconipyrone C.

Thiopyran route to polypropionates: exploiting and overcoming double stereodifferentiation and mutual kinetic enantioselection in aldol couplings of chiral fragments.

The aldol reaction of tetrahydro-4H-thiopyranone with 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde (I) gives four possible diastereomeric adducts (II). Aldol reactions of I with each of the diastereomers of II and their corresponding methoxymethyl ethers III via the Ti enolates were investigated. Using racemic reactants, reactions with II proceeded with high levels of mutual kinetic enantioselection (MKE) and double stereodifferentiation (DS) to give one of the eight possible bisaldol adducts. Similar reactions of III proceeded with low levels of MKE and DS and gave two bisaldol adducts, one from each of the possible combinations of enantiomeric reactants. By extension, 11 of the 20 possible diastereomers of the bisaldol adduct could be obtained selectively. These adducts are useful for polypropionate synthesis.

Thiopyran route to polypropionates: an efficient synthesis of serricornin.

The synthesis of serricornin [(4S,6S,7S)-7-hydroxy-4,6-dimethylnonan-3-one], a sex pheromone produced by the female cigarette beetle (Lasioderma serricorne F.), in seven steps from readily available racemic 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde (6) is described. The key steps include enantioselective aldol reaction of 6 with tetrahydrothiopyran-4-one catalyzed by 5-[(2S)-pyrrolidine-2-yl]-1H-tetrazole to fabricate the tetrapropionate skeleton, stereoselective Li(s)Bu(3)BH reduction of the resulting aldol adduct, Barton-McCombie deoxygenation, and Raney nickel desulfurization.

L-163,491 is a partial angiotensin AT(1) receptor agonist in the hindquarters vascular bed of the cat.

Responses to the nonpeptide angiotensin II agonist 5, 7-Dimethyl-2-ethyl-3-[[2'-([butyloxycarbonyl) aminosulfonyl]-5'-(3-methyoxybenzyl)-[1, 1'-biphenyl]-4-yl]methyl]-3H-imidazo[4,5-b]pyridine (L-163,491) were investigated and compared with responses to angiotensin II, angiotensin IV and norepinephrine in the hindquarters vascular bed of the cat under constant-flow conditions. Injections of L-163,491 into the hindquarter perfusion circuit caused dose-related increases in hindquarters perfusion pressure. In relative terms, angiotensin II was more potent than norepinephrine, which was more potent than angiotensin IV and L-163,491 in increasing hindlimb vascular resistance. The slope of the dose-response curve for L-163,491 was flat, while the apparent affinity of the compound for angiotensin AT(1) receptors was slightly greater than angiotensin IV. Responses to L-163,491 were inhibited by the angiotensin AT(1) receptor antagonist DuP 532 (2-propyl-4-pentafluoroethyl-1-[2'-(1H-tetrazol-5-yl)bipheny l-4-yl)me thyl]imidazole-5-carboxylic acid) and were not altered by the angiotensin AT(2) receptor antagonist PD123,319 (S(+)-1-[[4-(Dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl+ ++) -4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditribluoroacetate). However, the increase in hindlimb perfusion pressure in response to angiotensin II and angiotensin IV was significantly decreased following injection of L-163,491. These data suggest that the nonpeptide angiotensin analog L-163,491 has partial agonist activity, which is dependent on the stimulation of angiotensin AT(1) receptors in the hindquarters vascular bed of the cat.

Responding to the mental health needs of Latino children and families through school-based services.

This article highlights the value and utility of school-based mental health services in addressing the unmet mental health needs of Latino children and families in the United States. To better understand our nation's rapidly growing Latino population, such critical factors as demographic characteristics, cultural values, and family structure are examined. Special attention is devoted to the daunting challenges and resultant trauma experienced by many of these children and families who have recently immigrated to this country from war-torn home-lands in Central America. The mental health status of Latino children is addressed, along with various service delivery issues and psychotherapeutic modalities to facilitate their personal adjustment and social adaptation in a culturally sensitive manner. The article concludes with the presentation of an innovative school-based mental health program that offers a range of services of demonstrated effectiveness in aiding Latino children and their families. Specific strategies for replicating the program model in other culturally diverse settings are also discussed.

Optimizing the roles of school mental health professionals.

Each mental health discipline offers unique contributions to the development and operation of school-based mental health programs. The collaboration of professionals from different disciplines with each other, as well as with health and educational staff, is essential for service delivery in school settings. Conversely, interprofessional conflicts and turf issues can impede the development of effective school-based mental health programs. The authors, who represent counseling, nursing, psychiatry, psychology, and social work, discuss the roles and competencies of each profession in providing school-based mental health services. Training requirements within each discipline that relate to school mental health are described. Barriers to effective interdisciplinary collaboration, and methods of overcoming them, are delineated.

[Pro11,D-Ala12]angiotensin I has rapid onset vasoconstrictor activity in the cat.

Responses to the synthetic substrate [Pro11,D-Ala12]angiotensin I were investigated in the hindlimb vascular bed of the cat, a system in which local angiotensin-converting enzyme activity is high. Under constant-flow conditions, injections of [Pro11,D-Ala12]angiotensin I into the perfusion circuit in doses of 1-300 micrograms caused dose-related increases in perfusion pressure that were rapid in onset and that were not changed by the presence of a time-delay coil in the perfusion circuit upstream from the site of peptide injection. The synthetic substrate was approximately 100-fold less potent than angiotensin I and II, and responses to [Pro11,D-Ala12]angiotensin I were not altered by captopril in a dose that inhibited pressor responses to angiotensin I but did not alter responses to angiotensin II. Responses to [Pro11,D-Ala12]angiotensin I, angiotensin I, and angiotensin II were inhibited by DUP-532 and candesartan but were not altered by the angiotensin AT2 receptor antagonist PD-123319. The present data show that [Pro11,D-Ala12]angiotensin I has significant vasoconstrictor activity in the hindlimb vascular bed of the cat and suggest that responses are mediated by the activation of AT1 receptors and that activation of AT2 receptors is not involved. The present data show that the onset of responses to [Pro11,D-Ala12]angiotensin I and angiotensin II are similar and are not dependent on the action of the angiotensin-converting enzyme. The present data suggest that conversion of the synthetic substrate to an active peptide occurs rapidly within the hindlimb vascular bed or that the peptide may have direct AT1 receptor-stimulating activity.

Analysis of cardiovascular responses to PACAP-27, PACAP-38, and vasoactive intestinal polypeptide.

Responses to pituitary adenylate cyclase polypeptide (PACAP)-27, PACAP-38, and vasoactive intestinal peptide (VIP) were compared in the peripheral and pulmonary vascular beds of the cat and in the isolated perfused neonatal pig heart. Intravenous injections of PACAP-27 and PACAP-38 produced biphasic changes in systemic arterial pressure whereas iv injections of VIP caused only decreases in arterial pressure. When blood flow to the hind limb and mesenteric vascular beds was maintained constant, PACAP-27 and PACAP-38 caused dose-related biphasic changes in perfusion pressure, whereas VIP only decreased perfusion pressure. PACAP-27 was approximately threefold more potent than PACAP-38, and the pressor component of the biphasic response was blocked by alpha-adrenergic antagonists and adrenalectomy. PACAP-27, PACAP-38, and VIP produced decreases in pulmonary vascular resistance, and all three peptides had significant vasodilator activity in the isolated perfused neonatal pig heart. Although all three peptides decreased coronary vascular resistance, only PACAP-27 and PACAP-38 increased left ventricular contractility, with PACAP-27 approaching isoproterenol in potency. The results of these experiments show that PACAP-27, PACAP-38, and VIP have significant effects on vasomotor tone that depend on the vascular bed studied and the contribution of adrenal catecholamines.

Analysis of responses to angiotensin I and angiotensin I-(3-10) in the mesenteric vascular bed of the cat.

Responses to angiotensin I and antiogensin I-(3-10), the precursors for angiotensin II and IV, were investigated in the mesenteric vascular bed of the cat. Under constant-flow conditions, injections of precursors and the active peptides into the mesenteric arterial perfusion circuit caused dose-related increases in receptor antagonist that were attenuated by the angiotensin AT1 receptor antagonist DuP532 (2-propyl-4-pentafluorethyl-1-[2'-(2H-tetrazol-5-YL)-1,1'-bi phenyl-4-YL methyl]1H-imidazole-5-carboxylic acid), but not by the angiotensin AT2 receptor antagonist PD123,319 ((S)1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl )-4,5,6,7- tetrahydro-1H-imadazo[4,5-c]pyridine-6-carboxylic acid, ditriflouroacetate]). Responses to angiotensin I and II were similar as were responses to angiotensin I-(3-10) and angiotensin IV, and these responses were not altered by the presence of a time-delay coil in the perfusion circuit. Responses to angiotensin I and angiotensin I-(3-10) were decreased by the angiotensin converting enzyme inhibitor enalaprilat in a dose of the angiotensin converting enzyme inhibitor that had no effect on responses to angiotensin II and IV and that enhanced vasodilator responses to bradykinin. The putative angiotensin AT2 receptor agonist, p-aminophenylalanine6-angiotensin II, produced dose-related increases in mesenteric arterial perfusion pressure that were reduced by DUP532, suggesting that they are mediated by angiotensin AT1 receptors. These results suggest that angiotensin I and angiotensin I-(3-10) are rapidly and efficiently converted by an angiotensin converting enzyme-dependent pathway into active peptides that induce vasoconstriction by activating angiotensin AT1 receptors in the mesenteric vascular bed of the cat.

Analysis of responses to angiotensin I-(3-10) in the hindlimb vascular bed of the cat.

Responses to angiotensin I-(3-10), the precursor for angiotensin IV, were investigated in the anesthetized cat. Intravenous injections of the precursor caused dose-related increases in systemic arterial pressure that were similar to responses elicited by angiotensin i.v. and that were inhibited by captopril. in the hindlimb vascular bed of the cat under constant-flow conditions, injections of the substrate into the perfusion circuit in doses of 3-100 micrograms caused dose-related increases in hindlimb perfusion pressure that were rapid in onset and were not altered by the presence of a time-delay coil in the perfusion circuit. Dose-response curves for the precursor and angiotensin i.v. were parallel, and the precursor was approximately twofold less potent than angiotensin i.v. in its ability to increase hindlimb perfusion pressure. Responses to the precursor were inhibited by captopril in a dose that attenuated hindlimb vasoconstrictor responses to angiotensin I. Increases in hindlimb perfusion pressure in response to angiotensin I-(3-10) were inhibited by DuP-532 in a dose that attenuated the response to angiotensin i.v. PD-123,319, an AT2 receptor antagonist, had no significant effect on responses to angiotensin I-(3-10). The present results suggest that angiotensin I-(3-10) is rapidly and efficiently converted by an angiotensin converting enzyme-dependent pathway into an active peptide, which induces vasoconstriction by activating AT1 receptors in the peripheral vascular bed of the cat.

Analysis of responses to kallidin, DABK, and DAK in feline hindlimb vascular bed.

Responses to kallidin, des-Arg9-bradykinin (DABK), and des-Arg10-kallidin (DAK) were investigated in the hindlimb vascular bed of the cat under constant-flow conditions. Injections of kallidin, DABK, and DAK into the hindlimb perfusion circuit produced dose-dependent vasodilator responses in the hindlimb vascular bed. Vasodilator responses to kallidin and bradykinin (BK) were similar in magnitude and time course, and both peptides were approximately 100-fold more potent than DABK or DAK. Responses to kallidin were decreased by the kinin B2 antagonist, HOE 140, whereas responses to DABK and DAK were reduced by des-Arg9[Leu8]BK, a kinin B1-receptor antagonist. N omega-nitro-L-arginine methyl ester (L-NAME) reduced vasodilator responses to kallidin, DABK, and DAK, whereas meclofenamate, atropine, and U-37883A, a vascular selective ATP-sensitive K+ (K+ATP) channel-blocking agent, did not alter responses to the three peptides. These data suggest that both kinin B1 and B2 receptors are normally present in the hindlimb vascular bed. These data also suggest that kinin B1 and B2 receptor-mediated vasodilator responses are mediated by the release of nitric oxide and that the activation of K+ATP channels or muscarinic receptors, or the release of vasodilator prostaglandins play little if any role in mediating responses to kallidin, DABK, or DAK in the hindlimb vascular bed of the cat.

Analysis of responses to angiotensin peptides in the hindquarters vascular bed of the cat.

Responses to angiotensin I, II, III, and IV, des-Asp1-angiotensin I, and (p-amino-Phe6)-angiotensin II were compared in the hindquarters vascular bed of the cat. The peptides produced dose-related increases in perfusion pressure, and dose-response curves to all six peptides were parallel. Des-Asp1-angiotensin I, angiotensin I, II, and III produced similar increases in perfusion pressure and were approximately 300-fold more potent than (p-amino-Phe6)-angiotensin II, 100-fold more potent than angiotensin IV, 30-fold more potent than norepinephrine, and 10-fold more potent than U-46619. The time courses of the response to des-Asp1-angiotensin I, angiotensin I, II, and III were similar, and responses were not altered by a time-delay coil. DuP-532, an AT1 receptor antagonist, reduced responses to the six angiotensin peptides. PD-123,319 did not alter responses to the angiotensin peptides. The angiotensin-converting enzyme inhibitor captopril reduced responses to angiotensin I and des-Asp1-angiotensin I. These results show that des-Asp1-angiotensin I as well as angiotensin I, II, III, and IV have similar efficacy and that responses to the peptides and (p-amino-Phe6)-angiotensin II are mediated by AT1 receptors. These results suggest that AT2 receptors have little role in modulating responses and that angiotensin IV has a lower affinity for the AT1 receptor than does angiotensin II or III. The results also indicate that complete rapid local conversion of the substrates into active peptides occurs near the site of action within the hindquarters vascular bed.

Comparison of responses to adrenomedullin and adrenomedullin analogs in the mesenteric vascular bed of the cat.

Responses to adrenomedullin, a newly discovered hypotensive peptide isolated from human pheochromocytoma cells, and the carboxy terminal 15-52 (adrenomedullin-(15-52)) and 22-52 (adrenomedullin-(22-52)) amino acid fragments of adrenomedullin were investigated in the mesenteric vascular bed of the cat. Under constant flow conditions, injections of adrenomedullin, adrenomedullin-(15-52), and calcitonin gene-related peptide (CGRP) in doses of 0.003-1 nmol into the perfused superior mesenteric artery caused significant dose-related decreases in mesenteric arterial perfusion pressure. Mesenteric vasodilator responses to adrenomedullin and adrenomedullin-(15-52) were similar in magnitude and duration, while vasodilator responses to CGRP were greater in magnitude and longer in duration than those produced by adrenomedullin or adrenomedullin-(15-52) when these agents were injected in doses of 0.1-1 nmol. Adrenomedullin-(22-52) caused no significant change in mesenteric arterial perfusion pressure when injected in doses up to 10 nmol. These results suggest that amino acids 15-52 and the six-membered ring structure of adrenomedullin are important for the expression of vasodilator activity in the mesenteric vascular bed of the cat.

Analysis of responses to bradykinin: effects of Hoe-140 in the hindquarters vascular bed of the cat.

The mechanisms and receptor subtype mediating vasodilator responses to bradykinin were investigated in the hindquarters vascular bed of the cat under constant flow conditions. Intraarterial injections of bradykinin in doses of 10-1,000 ng into the hindquarters vascular bed caused dose-related decreases in perfusion pressure that were inhibited by Hoe-140, a bradykinin B2-receptor antagonist. Injections of des-Arg9-bradykinin (in doses 10-fold higher than for bradykinin) caused smaller dose-related decreases in hindquarters perfusion pressure that were not blocked by Hoe-140. Administration of atropine, glibenclamide, or cyclooxygenase inhibitors did not alter vasodilator responses to bradykinin, suggesting that activation of muscarinic receptors, ATP-sensitive K+ channels, or prostaglandin release is not involved in the response to the peptide. Administration of N omega-nitro-L-arginine and its methyl ester reduced vasodilator responses to bradykinin, acetylcholine, and substance P, whereas responses to endothelium-independent vasodilator agents were not attenuated. Decreases in systemic arterial pressure and in hindquarters perfusion pressure in response to bradykinin were enhanced by the angiotensin-converting enzyme inhibitors captopril and enalaprilat. These results suggest that hindquarters vasodilator responses to bradykinin are mediated by activation of kinin B2 receptors and in part by the release of nitric oxide. These data also suggest the presence of bradykinin B1 receptors, mediating vasodilation in the hindquarters vascular bed. These results indicate that bradykinin is rapidly inactivated by angiotensin-converting enzyme in the lung and in the hindquarters vascular bed of the cat.

Comparative effects of N omega-nitro-L-arginine and N omega-nitro-L-arginine methyl ester on vasodilator responses to acetylcholine, bradykinin, and substance P.

N omega-Nitro-L-arginine methyl ester has been reported to have muscarinic receptor blocking activity whereas the nonesterified analog does not bind to muscarinic receptors. The present study was, therefore, undertaken to compare the inhibitory effects of N omega-nitro-L-arginine methyl ester with those of N omega-nitro-L-arginine on baseline tone and on vasodilator responses to acetylcholine, bradykinin, and substance P in the mesenteric vascular bed of the cat under constant flow conditions. Administration of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine in doses of 100 mg/kg i.v. increased baseline tone in the mesenteric vascular bed and inhibited mesenteric vasodilator responses to acetylcholine, bradykinin, and substance P. The increase in mesenteric arterial perfusion pressure and the decrease in vasodilator responses to the three endothelium-dependent vasodilator agents following administration of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine did not differ significantly. The nitric oxide synthase inhibitors did not attenuate vasodilator responses to agents that induce vasodilation by nonendothelium-dependent mechanisms and enhanced responses to the nitrovasodilators. Atropine blocked vasodilator responses to acetylcholine but did not alter responses to bradykinin or substance P. The similarity in the inhibitory effects of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine on responses to acetylcholine, bradykinin, and substance P suggest that the L-arginine analog, N omega-nitro-L-arginine, as well as the methyl ester of N omega-nitro-L-arginine, are useful probes for studying endothelium-dependent vasodilator responses in the mesenteric vascular bed of the cat.