Renal vascular reactivity to vasopressin in rats with diabetes mellitus.

We evaluated how renal vascular reactivity to vasopressin changes when nitric oxide (NO) synthesis varies, as has been reported to occur in the course of insulin-dependent diabetes mellitus. Renal vasoconstrictor responses to vasopressin were obtained in young and older Sprague-Dawley control rats (3 and 10 months old) and in age-matched diabetic rats that had been treated with streptozotocin (60 mg/kg i.v.) at the age of 2 months. In young rats, vasopressin (3-1000 ng/kg/min i.v.) induced in vivo a dose-dependent decrease in renal blood flow, which was diminished in streptozotocin diabetic rats (P<0.05). Similarly, in in vitro perfused kidneys, the concentration-response curve for vasopressin (0.03-10 nM) was shifted 3-fold to the right in kidneys isolated from young diabetic rats (P<0.05). This shift was abolished in the presence of an inhibitor of nitric oxide synthesis, N(G)-nitro-L-arginine (100 microM), in the perfusate. In 10-month-old rats, the in vivo renal vasoconstrictor dose-response curve to vasopressin was shifted 10-fold to the left as compared to that for young rats (P<0.001). This shift was similar in both control and diabetic rats.In conclusion, the present study documented the existence of hyporesponsiveness to vasopressin in the early stage of diabetes, possibly related to nitric oxide overproduction. In contrast, renal vascular hyperreactivity to vasopressin occurs with aging, whether the rats are diabetic or not.     

Vascular reactivity in diabetes mellitus: role of the endothelial cell.

The response to vasoactive agents of microvessels in situ and large arteries in vitro was compared in normal and alloxan-diabetic rats. Noradrenaline was equally effective in evoking a constrictor response of mesenteric microvessels in normal and diabetic animals. The constrictor response to a standard amount of noradrenaline in such vessels was fully antagonized by acetylcholine or papaverine, the minimum effective doses being equivalent in normal and diabetic animals. In contrast, the minimum doses of histamine or bradykinin, effective in normal animals, had to be increased about 20 fold to be active in diabetic animals. Increased osmolarity of extracellular fluid caused a significant and equivalent increase in latency of the vasoconstrictor response of microvessels to noradrenaline in normal and diabetic animals. Concentration-effect curves, constructed from the response of isolated aortae to noradrenaline, were similar in normal and diabetic animals, provided the endothelium was removed. Diabetes only affected preparations in which the endothelium was left intact. In these, the median effective concentrations of noradrenaline were greatly increased in comparison with normal values. Precontracted aortae from normal and diabetic animals were equally relaxed by acetylcholine and histamine, provided the endothelium was left intact. Loss of the relaxant response of the preparations in all groups of animals was observed following removal of endothelial cells. It is suggested that different mechanisms may be involved in the effects of vasodilator agents on large arteries in vitro or small vessels in situ. Histamine and bradykinin which are potent permeability-increasing factors, may antagonize the vasoconstrictor response of microvessels to noradrenaline through an action on endothelial cells with increased vascular permeability and temporary changes in composition of extracellular fluid. The reactive process of endothelial cells to permeability factors was affected by diabetes mellitus. However, the response of microvessels to acetylcholine and papaverine which are devoid of permeability-increasing properties, was not influenced by diabetes.     

Enhanced reactivity to vasopressin in rat basilar arteries during vasospasm after subarachnoid hemorrhage

Subarachnoid hemorrhage increases the plasma level of vasopressin, a well-known vasoconstrictor. We examined the sensitivity to vasopressin in rat basilar artery after subarachnoid hemorrhage using a rat subarachnoid hemorrhage model. Vasospasm was observed 1-2 days after subarachnoid hemorrhage induction, and the contractile response to vasopressin in rat basilar arteries was assessed. The concentration-response curve for vasopressin in subarachnoid hemorrhage (1 day) rats shifted leftward compared with that of control rats. The concentration-response curve for vasopressin V(1) receptor agonist also shifted leftward and upward compared with that of control rats. The concentration-response curve for vasopressin was inhibited not by vasopressin V(2) receptor antagonist but by vasopressin V(1) receptor antagonist. Thus, it was demonstrated that the vasoconstricting effect of vasopressin was significantly enhanced in the vasospasm phase after subarachnoid hemorrhage.     

Vascular reactivity in diabetes mellitus: possible role of insulin on the endothelial cell

The response to vasoactive agents of microvessels of the rat was tested in vivo by direct microscopic observation of the exteriorized mesentery and assessment of cutaneous vascular permeability changes with Evans blue. The constrictor response to a standard amount of noradrenaline in mesenteric microvessels was fully antagonized by acetylcholine in normal, diabetic, adrenalectomized and diabetic-adrenalectomized rats. In contrast, the minimum doses of histamine or bradykinin, effective in normal or adrenalectomized animals, had to be increased about 20 fold to be active in diabetic or diabetic-adrenalectomized animals. Topical application of insulin to mesenteric microvessels of diabetic animals, in amounts not causing any increase in serum insulin levels, improved or restored the capacity of the animals to respond to histamine or bradykinin, acting as antagonists of the vasoconstrictor response to noradrenaline. Topical insulin, however, was ineffective in normal animals given 2-deoxyglucose, the acute effects of which result from cellular glucopaenia unrelated to insulin deficiency. Vascular permeability responses to intracutaneous histamine or bradykinin were decreased in animals pretreated with 2-deoxyglucose as much as in diabetic animals. Pretreatment of normal animals with indomethacin produced no effect on the responses of these animals to histamine or bradykinin, tested as antagonists of noradrenaline on mesenteric microvessels, or as vascular permeability-increasing factors in the skin. Pretreatment of normal animals with chloroquine, mepacrine or dexamethasone had no effect on the reactivity of mesenteric microvessels to histamine and bradykinin, acting as antagonists to noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vascular reactivity to 5-hydroxytryptamine and hypertension in the rat

Summary Isolated perfused mesenteric artery preparations of genetic (Japanese strain), renal and DOCA/saline hypertensive rats showed a marked increase in reactivity to the vasoconstrictor effect of 5-hydroxytryptamine (5-HT) as compared with normotensive controls. In the arteries of the hypertensive animals, the threshold vasoconstrictor doses of 5-HT were lower, the 5-HT dose-response curves were steeper and their maxima were increased by a factor of 2.5–4.2. These observation only partially fit into the concept that increased vascular reactivity in hypertension is due to an increased wall/lumen ratio of the arterial blood vessels. Pressor responses to 5-HT were also higher in isolated perfused hindquarter and in pithed preparations from renal and DOCA/saline hypertensive rats but not in those from genetic hypertensive rats. In isolated perfused renal artery preparations, the reactivity to 5-HT was equal for normotensive and hypertensive (genetic and DOCA/saline) animals, indicating that not all arteries of hypertensive rats share the increased reactivity to 5-HT. Pretreatment with reserpine slightly reduced the reactivity to 5-HT in arteries from both hypertensive and normotensive rats. Non-vascular smooth muscle of DOCA/saline hypertensive rats, for which isolated gastric strips were used as an example, responded to 5-HT in the same way as that of normotensive rats. Methysergide blocked the pressor responses to 5-HT but did not influence the blood pressure of the hypertensive animals, thus questioning a causal relationship between the increased vascular reactivity to 5-HT and the maintenance of high blood pressure in these three types of experimental hypertension.Preliminary results have been presented at the 3rd Meeting of the Union of the Swiss Societies for Experimental Biology in Zurich (Haeusler and Finch, 1971).     

Vascular reactivity to methoxamine in conscious sinoaortic denervated rats

Alterations in vascular alpha-adrenoceptor responsiveness following sinoaortic denervation was studied in conscious rats. The arterial hypertension observed in baroreceptor denervated rats decreased progressively during the 30 days of observation. A pressor hyperresponsiveness to methoxamine (10-80 micrograms/kg, iv), was observed 3 to 7 days after baroreceptor denervation followed by a gradual normalization of the vascular reactivity. The results indicate a possible participation of an enhanced alpha 1-adrenoceptor-mediated vasoconstrictor component in the early phase of neurogenic hypertension.     

Conditioned taste aversion and alcohol drinking: strain and gender differences

OBJECTIVE: The present study examined the relationship between ethanol-induced conditioned taste aversion (CTA) and ethanol oral self-administration (OSA) in male and female rats (N = 183) from three related strains not genetically selected for their ethanol preference and differing in their emotional reactivity profile. The strains used were the Wistar Kyoto (WKY), Spontaneously Hypertensive (SHR) and Wistar Kyoto Hyperactive (WKHA). We hypothesized that differences between strains in sensitivity to the aversive properties of alcohol could explain the different propensities to drink alcohol solutions. METHOD: All animals were given three conditioning trials consisting of 20-minute access to saccharin solution followed by saline or ethanol injections (0.5, 1 or 1.5 g/kg, intraperitoneally). Animals subsequently had free access to ethanol OSA for 3 weeks, followed by two CTA trials. RESULTS: Ethanol injections produce a dose-dependent reduction of saccharin consumption in all animals; moreover, the strength of the CTA is gender- and strain-dependent. Taste avoidance induced by ethanol injections disturbed the initiation of ethanol OSA in two strains (WKY and WKHA) but did not change subsequent long-term ethanol consumption in either strain. In addition, voluntary alcohol drinking experience does not attenuate ethanol-induced CTA, and no association was found between ethanol-induced CTA and ethanol OSA. CONCLUSIONS: The data confirm the large variation among strains and between genders in alcohol drinking and taste-aversion learning, but suggest that there is no relationship between the sensitivity to the aversive properties of alcohol and alcohol drinking.     

The immunobiology of sexual behavior: gender differences in the suppression of sexual activity during illness

Following infection or injury, sick individuals experience profound psychological and behavioral changes, such as anorexia, depressed activity, and reduced self-care behavior. In the present review, we present evidence for a gender-difference in the behavioral response to sickness. Specifically, following immune activation, sexual activity is suppressed in female, but not in male rats. This gender difference is specific to sexually related responses, because other behaviors, such as locomotion, are equally affected by immune challenges in males and estrous females. The suppression of female sexual behavior, induced by either endotoxin (lipopolysaccharide), or the cytokine interleukin-1 (IL-1), are mediated by central mechanisms that are independent of alterations in ovarian hormone secretion. Furthermore, synergistic effects of the cytokines IL-1 and tumor necrosis factor alpha (TNF alpha) are involved in modulating sexual behavior in sick females, and prostaglandins synthesis is required for the effects of IL-1 on female sexual behavior. The gender difference in the behavioral response to immune activation may be related to the findings that at the same doses and timing in which IL-1 suppressed sexual activity in female but not in male rats, females produced more prostaglandin E2 (PGE2) in the brain, and less corticosterone than males. Finally, we are suggesting that the suppressive effect of cytokines on female reproductive behavior may serve as a mechanism to reduce conception during infection, which exposes the mother and the fetus to dangers such as spontaneous abortions, preterm labor and maternal mortality.     

Sexual and gender minority young adults' smoking characteristics: Assessing differences by sexual orientation and gender identity

IntroductionSexual and gender minority (SGM) young adults have higher smoking prevalence than their non-SGM peers. Less is known about differences in smoking characteristics within the SGM community.MethodsParticipants were SGM young adult smokers age 18–25 (N = 165, M age = 21.8) enrolled in a clinical trial of the Put It Out Project, a Facebook smoking cessation intervention for SGM young adults. Analyses tested differences between 1) sexual orientation groups, and 2) gender identity groups, on the following smoking characteristics: cigarettes/day, daily smoker (yes/no), social smoker (yes/no), years of smoking, number of close friends who smoke (out of 5), age of initiation, age began smoking regularly, time to first cigarette (30 min or less/>30 min), lifetime quit attempts, past-year quit attempts, and stage of change for quitting smoking (precontemplation, contemplation, preparation).ResultsParticipants were 56% bi/pansexual, 18% gay, 18% lesbian, 8% other (e.g., asexual, queer). The gender identity of the sample was 52% cisgender, 18% transgender, 30% gender non-binary. Lesbian women began smoking at an older age (M = 18.0, SD = 2.0) than “other” sexual orientation participants (M = 15.7, SD = 2.2), p < .05. Transgender participants smoked the most cigarettes per day (M = 11.3, SD = 6.7), followed by cisgender (M = 8.1, SD = 5.6), then non-binary (M = 5.7, SD = 3.5) participants (p < .001; pairwise comparisons p's < 0.05). No other constructs differed by sexual orientation or gender.ConclusionsSmoking characteristics were mostly similar across subgroups of young adult SGM smokers; however, transgender individuals were heavier smokers.     

Health and performance related reasons for wanting to quit: gender differences among teen smokers

Adolescents frequently state health as a broad-ranging reason for wanting to quit smoking. Much less is known regarding performance-related reasons. We hypothesized that more male than female smokers want to quit for performance-related reasons (e.g., to improve athletic performance). As part of a telephone screen to determine eligibility for participation in a cessation trial in Baltimore, Maryland, 1999-2001, 509 teenage smokers [mean age 15.78 +/- 1.65 years (range 11-21), 60.9% female, 32.6% African-American] were asked the open-ended question: "Why do you want to quit?" Responses were subsequently grouped into categories that included health, performance, cost, social influences, setting an example for others, self-efficacy, cosmetics, no perceived positive reinforcement, or unknown reasons. Health was the most commonly stated primary and overall reason for wanting to quit among both boys and girls. Sixty-five percent of teen smokers endorsing health reasons were girls, and 51% of those endorsing performance-related reasons were boys (chi2(2) = 7.78, p = 0.02). Recognizing the greater concern for performance-related issues among boys is important for designing and engaging young smokers into cessation interventions.     

Regional differences in the arterial response to vasopressin: role of endothelial nitric oxide.

1. The isometric response to arginine-vasopressin (10(-10)-10(-7)M) was studied in 2 mm long rabbit arterial segments isolated from several vascular beds (cutaneous, pial, renal, coronary, muscular, mesenteric and pulmonary). 2. Vasopressin induced contraction in central ear (cutaneous), basilar (pial), renal, coronary and saphenous (muscular) arteries, but had no effect in mesenteric and pulmonary arteries; the order of potency for the contraction was: ear > basilar > renal > coronary > saphenous arteries. 3. Treatment with the blocker of nitric oxide synthesis NG-nitro-L-arginine methyl ester (L-NAME; 10(-6)-10(-4) M) increased significantly (P < 0.05) the contraction to vasopressin in ear (148% of control), basilar (150% of control), renal (304% of control), coronary (437% of control) and saphenous (235% of control) arteries. Removal of the endothelium increased significantly (P < 0.05) the contraction to vasopressin in basilar (138% of control), renal (253% of control), coronary (637% of control) and saphenous (662% of control) arteries, but not in ear artery. Mesenteric and pulmonary arteries in the presence of L-NAME or after endothelium removal did not respond to vasopressin, as occurred in control conditions. 4. The specific antagonist for V1 vasopressin receptors d(CH2)5Tyr(Me)AVP (3 x 10(-9)-10(-7) M) was more potent (pA2 = 9.3-10.1) than the antagonist for both V1 and V2 vasopressin receptors desGly-d(CH2)5-D-Tyr(Et)ValAVP (10(-7)-10(-6) M) (pA2 = 7.4-8.4) to block the contraction to vasopressin of ear, basilar, renal and coronary arteries. 5. The specific V2 vasopressin agonist [deamino-Cys1, D-Arg8]-vasopressin (desmopressin) (10(-10)-10(-7) M) did not produce any effect in any effect in any of the arteries studied, with or without endothelium. 6. In arteries precontracted with endothelin-1, vasopressin or desmopressin did not produce relaxation. 7. These results suggest: (a) most arterial beds studied (5 of 7) exhibit contraction to vasopressin with different intensity; (b) the vasoconstriction to this peptide is mediated mainly by stimulation of V1 vasopressin receptors, and (c) endothelial nitric oxide may inhibit the vasoconstriction to this peptide, especially in coronary and renal vasculatures.     

Smoking cue reactivity across massed extinction trials: negative affect and gender effects

Designing and implementing cue exposure procedures to treat nicotine dependence remains a challenge. This study tested the hypothesis that gender and negative affect (NA) influence changes in smoking urge over time using data from a pilot project testing the feasibility of massed extinction procedures. Forty-three smokers and ex-smokers completed the behavioral laboratory procedures. All participants were over 17 years old, smoked at least 10 cigarettes daily over the last year (or the year prior to quitting) and had expired CO below 10 ppm at the beginning of the ~4-hour session. After informed consent, participants completed 45 min of baseline assessments, and then completed a series of 12 identical, 5-minute exposure trials with inter-trial breaks. Smoking cues included visual, tactile, and olfactory cues with a lit cigarette, in addition to smoking-related motor behaviors without smoking. After each trial, participants reported urge and negative affect (NA). Logistic growth curve models supported the hypothesis that across trials, participants would demonstrate an initial linear increase followed by a decrease in smoking urge (quadratic effect). Data supported hypothesized gender, NA, and gender×NA effects. Significant linear increases in urge were observed among high and low NA males, but not among females in either NA subgroup. A differential quadratic effect showed a significant decrease in urge for the low NA subgroup, but a non-significant decrease in urge in the high NA group. This is the first study to demonstrate gender differences and the effects of NA on the extinction process using a smoking cue exposure paradigm. Results could guide future cue reactivity research and exposure interventions for nicotine dependence.     

Cue reactivity in smokers: the effects of perceived cigarette availability and gender

We examined the effects of perceived cigarette availability and gender on smoking cue reactivity. Smokers were exposed to smoking cues (smoking paraphernalia) and control cues whilst their subjective and physiological responses were measured. Perceived cigarette availability was manipulated on a between-subjects basis before cue exposure. Relative to control cues, smoking cues evoked increases in the level of skin conductance in all participants. Cigarette craving was also increased in the presence of smoking cues, but only in female participants. Perceived cigarette availability had no effect on these responses. Participants also showed salivary reactivity to smoking cues, with males showing a decrease in salivation, and females showing an increase, but only when cigarettes were perceived as unavailable. These results suggest that perceived cigarette availability may not influence craving and skin conductance reactivity to smoking cues in minimally dependent smokers who are not nicotine deprived. In addition, the present data suggest that there are important gender differences in craving reactivity to smoking cues.     

Drug abuse and dependency: understanding gender differences in etiology and management

OBJECTIVE: To review the etiology, consequences, and treatment needs of drug abuse and dependency, especially in women. DATA SOURCES: Original studies and literature reviews published primarily since 1990. DATA SYNTHESIS: Many studies, conducted mostly during the past 10 years, are providing new information regarding the genesis of two separate drug problems: willful abuse (misuse) of drugs and pathological drug dependency. Recent studies have also highlighted important differences between the sexes in the causes, consequences, and management of drug abuse and dependency. The neurobiologic and genetic contributions to the pathological disease of addiction provide important directions for future treatments, as a supplement to existing self-help and structured behavioral therapies. Pharmacotherapy also has an important role in reducing drug craving and relapse in addicted patients. CONCLUSION: Although the precise causes of drug abuse and dependency continue to challenge researchers, important differences have been identified between men and women in terms of how drug use begins, how it progresses, and effective methods of treatment. Pharmacists and other health care professionals need to understand gender differences in the etiology and management of drug abuse and dependency and develop the capacity to recognize and refer women who may be abusing or dependent on drugs.     

Vascular reactivity in spontaneously hypertensive normotensive and hypotensive rats

1 Three strains of rats spontaneously hypertensive (HRS), normotensive (NS) and hypotensive (HOS), were selected by repeated inbreeding.2 In order to explain the different blood pressure levels observed, we have studied their vascular reactivity to noradrenaline and angiotensin II. Experiments were performed in anaesthetized ganglion-blocked, vagotomized rats.3 The reactivity to noradrenaline was significantly higher in HRS than in NS and HOS rats.4 The reactivity to angiotensin II appeared identical in the three strains used.