ABSTRACT
The role of ANG II in the arterial baroreflex control of renal sympathetic nerve activity (RSNA) in eight term-pregnant (P) and eight nonpregnant (NP) conscious rabbits was assessed using sequential intracerebroventricular and intravenous infusions of losartan, an AT1 receptor antagonist. The blood pressure (BP)-RSNA relationship was generated by sequential inflations of aortic and vena caval perivascular occluders. Pregnant rabbits exhibited a lower maximal RSNA reflex gain (-44%) that was primarily due to a reduction in the maximal sympathetic response to hypotension (P, 248 +/- 20% vs. NP, 357 +/- 41% of rest RSNA, P < 0.05). Intracerebroventricular losartan decreased resting BP in P (by 9 +/- 3 mmHg, P < 0.05) but not NP rabbits, and had no effect on the RSNA baroreflex in either group. Subsequent intravenous losartan decreased resting BP in NP and further decreased BP in P rabbits, but had no significant effect on the maximal RSNA reflex gain. ANG II may have an enhanced role in the tonic support of BP in pregnancy, but does not mediate the gestational depression in the arterial baroreflex control of RSNA in rabbits.
Subject(s)
Baroreflex/physiology , Pregnancy, Animal/physiology , Receptors, Angiotensin/metabolism , Angiotensin II/antagonists & inhibitors , Angiotensin II/blood , Angiotensin II/pharmacology , Angiotensin Receptor Antagonists , Animals , Antihypertensive Agents/pharmacology , Aorta/physiology , Baroreflex/drug effects , Blood Pressure/drug effects , Blood Pressure/physiology , Female , Injections, Intravenous , Injections, Intraventricular , Losartan/pharmacology , Pregnancy , Rabbits , Receptor, Angiotensin, Type 1 , Receptor, Angiotensin, Type 2 , Rest/physiology , Sympathetic Nervous System/physiology , Vasoconstrictor Agents/antagonists & inhibitors , Vasoconstrictor Agents/blood , Vasoconstrictor Agents/pharmacologyABSTRACT
Saccharomyces cerevisiae telomeric DNA replicates late in S phase, and telomeric genes are transcriptionally silent. Transcriptional repression of telomere-proximal genes results from silent chromatin initiating at the chromosome end, but the relationship between telomeric chromatin and DNA replication is unknown. Mutations in SIR3, a silent chromatin component, cause telomeric DNA on chromosome V to replicate much earlier because of earlier initiation of a nearby replication origin, the Y' ARS. A second telomere-proximal ARS, from an X element, does not act as an origin in a wild-type strain, whereas in a sir3 cell it does. We conclude that telomeric chromatin has a Sir3-dependent inhibitory effect on DNA replication.
Subject(s)
Chromatin/genetics , DNA Replication/genetics , Fungal Proteins/metabolism , Saccharomyces cerevisiae/genetics , Silent Information Regulator Proteins, Saccharomyces cerevisiae , Telomere/genetics , Trans-Activators/metabolism , Fungal Proteins/genetics , Mutation , Replication Origin/genetics , Repressor Proteins/metabolism , S Phase , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/metabolism , Time Factors , Trans-Activators/genetics , Transcription, Genetic/geneticsABSTRACT
Female Sprague-Dawley rats were administered fentanyl continuously using chronically implanted osmotic minipumps for 2 weeks before breeding and during the entire period of pregnancy. Three different fentanyl dosage regimens were employed, i.e., 10, 100, and 500 micrograms/kg/day. Reproductive indices were determined and the 1,046 offspring delivered at cesarean section were examined for external, visceral, and skeletal abnormalities. There were no major or minor reproductive abnormalities or teratogenic findings in any of the fentanyl-treated groups. We conclude that fentanyl is devoid of adverse reproductive effects in this strain of rats up to dosages of 500 micrograms/kg/day administered by osmotic minipumps. From a methodologic point of view, osmotic minipumps facilitate study of the reproductive effects of narcotics as they allow delivery of dosages that ordinarily would not be tolerated without producing severe respiratory depression.
