Male mice produce scent marks by depositing urine throughout their territory. The scent marks contain a number of pheromones and contain major urinary proteins (MUPs). Up to 1 g of these MUPs may be produced everyday. It is therefore likely that scent marking is costly and as such will impact on male fitness. In order to investigate the costs of scent marking, we conducted an experiment where scent marking rate was increased artificially, without changing the social environment (which may have an independent and different effect on both scent marking and physiology), or changing travelling time (such as would occur in a larger territory). Novel objects were introduced every other day (Replace); objects were introduced on day 1 and moved on alternate days (Move); or the mice were left undisturbed (Control). Introducing new objects daily caused a significant increase in scent marking rate, and an increase in the size of both the coagulating gland and the testes compared to the other two conditions. This is likely to be due to increased hormonal activity, which is known to affect these gland sizes. Interestingly, the preputial gland, which produces a number of pheromones, did not differ between the three conditions. There were no differences in male weight, growth rate or condition, indicating that the effect of an increase in scent marking of this magnitude does not have measurable fitness effects.

Animal Communication↗

PubMedDate not supplied

Antihypertensive activity of SCH 31846, a non-sulfhydryl angiotensin-converting enzyme inhibitor.

The antihypertensive, hemodynamic, and autonomic actions of SCH 31846, a new, potent and long-acting non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor, were evaluated in several experimental preparations. Oral administration of 0.3-3 mg/kg caused dose-related decreases in blood pressure in spontaneously hypertensive rats (SHRs). Pretreatment with a diuretic augmented the maximum hypotensive response attainable. Single doses (3 mg/kg) of SCH 31846 reduced pressure for over 24 h. Five-day treatment lowered pressure progressively. Single oral doses of 3.2 and 10 mg/kg reduced blood pressure of conscious normotensive dogs. Diuretic pretreatment also enhanced the response. The antihypertensive action of SCH 31846 in SHRs was eliminated by nephrectomy, but not attenuated by indomethacin, indicating its dependency on renal renin but not on prostaglandin synthesis. Other studies using SHRs pointed to an absence of a central effect. SCH 31846 (1 mg/kg i.v.) decreased blood pressure and peripheral resistance of anesthetized dogs but did not alter cardiac output. Autonomic interactions were examined in normal and diuretic-pretreated SHRs and anesthetized dogs. SCH 31846 affected the response to sympathetic nerve stimulation and cardiovascular reflexes only minimally. It is concluded that SCH 31846 is a potent and long-lasting antihypertensive agent, the action of which is mediated, in all probability, by ACE inhibition.

Angiotensin-Converting Enzyme Inhibitors↗

PubMedDate not supplied

Hemodynamic actions of a synthetic atrial natriuretic factor.

The recently discovered atrial natriuretic factor (ANF), as well as synthetic ANF, has been demonstrated to produce diuresis and vasodilation. However, the vascular actions appear to be selective. In view of this apparent relative specificity, the hemodynamic actions of synthetic ANF (atriopeptin II, 23 amino acid rat sequence) were examined in intact animals and in vascular beds as well as in isolated cardiac preparations. Administration of 1-100 micrograms/kg of ANF i.v. into conscious spontaneously hypertensive rats (SHRs) resulted in a dose-related fall in blood pressure. Heart rate decreased at the lowest dose. Cardiac output was depressed. Infusion of 1 microgram/kg/min also reduced blood pressure and decreased cardiac output slightly (approximately 15%). Intraarterial (i.a.) administration or i.v. injection of ANF into the blood supply of a kidney of anesthetized SHRs augmented renal blood flow and reduced renal vascular resistance. In contrast, i.a. administration into the hindquarters failed to increase blood flow or decrease resistance of this bed significantly. The specific dopamine1 (DA1)-receptor agonist SKF 82526 was examined for comparative purposes and was found to augment both renal and hindquarter blood flow following i.a. administration. The renal vasodilator actions of SKF 82526 but not ANF were antagonized by the specific DA1-receptor blocker SCH 23390 (hindquarter effects were not evaluated). ANF did not affect the force of contraction or rate of beating of isolated guinea pig atria or isolated hearts and therefore does not appear to possess direct inotropic or chronotropic properties. In conclusion, ANF lowered blood pressure in conscious SHRs; the lowering of pressure was accompanied by a slight fall in cardiac output, but there was no reflex tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Role of beta 2-receptor stimulation in the peripheral vascular actions of the antihypertensive dilevalol.

Dilevalol (SCH 19927) is a potent, long-acting, nonselective beta-blocker with marked vasodilator actions. Unlike classical beta-blockers, dilevalol promptly lowers blood pressure and vascular resistance in animal models of hypertension. The present studies address the peripheral vascular effects of dilevalol and explore the role of beta-receptor agonism in the acute vasodilator and antihypertensive effects of the compound. In the denervated dog hindlimb preparation, dilevalol (0.1, 0.3, 1.0 and 3.0 micrograms, i.a.) significantly increased femoral blood flow by 12 +/- 6, 27 +/- 6, 84 +/- 31 and 132 +/- 41 ml/min, respectively. In contrast, celiprolol, a beta-blocker with purported vasodilator activity, caused a significant increase in flow of 31 +/- 9 ml/min at a dose of 30 micrograms i.a. Systematic pretreatment with the selective beta 2-antagonist ICI 118,551 virtually abolished dilevalol's vasodilator effect in the dog hindlimb. In conscious spontaneously hypertensive rats, 3 mg/kg i.v. dilevalol reduced blood pressure by 58 +/- 8 mmHg (P less than 0.05) and vascular resistance by 171 +/- 27 dyne.sec.cm-5/100 g (P less than 0.05) but did not change cardiac output significantly. Pretreatment of spontaneously hypertensive rats with ICI 118,551 significantly reduced both dilevalol's antihypertensive and resistance-lowering effects. Oral doses of 10 and 25 mg/kg dilevalol lowered blood pressure by 19 +/- 3 (P less than 0.05) and 37 +/- 5 mmHg (P less than 0.05) in spontaneously hypertensive rats with chronically implanted Doppler flow probes. The lower dilevalol dose reduced mesenteric vascular resistance 38 +/- 6% (P less than 0.05) while the higher dose significantly lowered vascular resistance in the hindlimb, mesenteric and renal vascular beds of spontaneously hypertensive rats by 18 +/- 8, 33 +/- 2 and 43 +/- 4%, respectively. Propranolol lowered neither blood pressure nor regional vascular resistances at the above doses in spontaneously hypertensive rats. Thus, dilevalol promotes a generalized fall in vascular resistance. Furthermore, the present studies illustrate that beta 2-receptor stimulation plays an obligatory role in both the vasodilatory and antihypertensive actions of dilevalol.

Adrenergic beta-Agonists↗

PubMedDate not supplied

Comparative effects of verapamil, diltiazem and nifedipine on aortic compliance in anesthetized dogs.

We tested the ability of verapamil (V), diltiazem (DTZ) and nifedipine (NIF) to alter aortic compliance upon i.v. administration in anesthetized dogs. Sonomicrometry was used to measure aortic systolic (SD) and diastolic (DD) diameters. Aortic distention (AD) was calculated from SD-DD. Aortic compliance was computed from the ratio of AD to arterial pulse pressure. One aortic compliance unit (ACU) is defined as 10(-3) mm/mmHg. V (0.1-3.0 mg/kg) reduced blood pressure, SD and DD dose-dependently. DD was more affected than SD and AD rose significantly. Since pulse pressure was not significantly altered, V induced a dose-related increase in aortic compliance. The 3.0 mg/kg dose increased aortic compliance by 10.3 +/- 1.5 ACU from a basal value of 4.7 +/- 0.5 ACU. DTZ (0.1-3.0 mg/kg) produced effects on blood pressure, aortic dimensions and aortic compliance similar to those seen with V. Infusion of NIF (3.2-32 micrograms/kg/min) exhibited a similar profile, i.e., reduced blood pressure, SD, DD and increased AD and aortic compliance. NIF, however was limited in its ability to increase aortic compliance, i.e., increases of 3.2 +/- 1.0 or 3.8 +/- 0.6 from basal values of 4.9 +/- 1.0 ACU were obtained with 10 and 32 micrograms/kg/min NIF, respectively. Although these 3 prototype calcium entry blockers share a common profile of action, V and DTZ appear to have a greater efficacy on aortic compliance than NIF.

Anesthesia↗