Biomedical subjects

W S Quirk

Publications and source records attributed to W S Quirk.

58 records · Page 4Linked to original sources

PubMed1987

Amastatin and bestatin-induced dipsogenicity in the Sprague-Dawley rat.

Intracerebroventricular application of the aminopeptidase inhibitor bestatin, but not amastatin, demonstrated a dose-dependent drinking response. Amastatin is a selective, but not totally specific aminopeptidase inhibitor that blocks aminopeptidase A, which cleaves acidic amino acids, while bestatin selectively blocks aminopeptidase B, which cleaves basic amino acids. Thus, amastatin's major action should be to inhibit angiotensin II (AII) to angiotensin III (AIII) conversion and bestatin's to block AIII degradation. Treatment with the angiotensin receptor antagonist, Sar, Thr-AII (sarthran), completely inhibited bestatin-induced drinking at two different doses. These results support a critical role for the brain-angiotensin system in the ongoing regulation of body fluid homeostasis and suggest an important role for angiotensin III in the brain.

Aminopeptidases↗

PubMed1986

Heightened pressor effect and dipsogenicity to intracerebroventricularly applied angiotensin II and III in spontaneously hypertensive rats.

The effect of acute intracerebroventricular (i.c.v.) injections of angiotensin II and III (ANG II and ANG III; 0, 1, 10 and 100 pmol in 2 microliters artificial cerebrospinal fluid (CSF) on blood pressure and water consumption was investigated in Okamoto-Aoki spontaneously hypertensive rats (SHR), and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) normotensive controls. Heightened sensitivity to i.c.v. ANG II and ANG III was observed in the SHR compared with the WKY and SD strains (P less than 0.001), for both pressor and drinking responses. In addition, i.c.v. treatment with an aminopeptidase B inhibitor, bestatin (20 nmol in 1 microliter artificial CSF) significantly potentiated the heightened pressor response to i.c.v.-injected ANG II and ANG III (100 pmol) in SHR and to a lesser degree in WKY animals compared with SD controls (P less than 0.001). These results suggest that a dysfunction in central aminopeptidase activity results in an extended life of endogenous angiotensins, and perhaps other peptides that may contribute to the high blood pressure seen in this animal model of human essential hypertension.

Angiotensin II↗

PubMedDate not supplied

Brain angiotensin: critical role in the ongoing regulation of body fluid homeostasis and cardiovascular function.

The existence of an endogenous brain-angiotensin system and its association with cardiovascular and body water regulation has been recognized for over a decade. Nevertheless, the importance of the brain-angiotensin system to the instantaneous regulation of these processes has not been firmly established. A 5-minute intracerebroventricular (ICV) infusion of the angiotensin antagonist, [Sar1,Thr8]-AII, effectively lowered the blood pressure in normotensive rats. Additionally, application of the selective aminopeptidase inhibitor, bestatin, given alone, resulted in a dramatic increase in blood pressure and a robust drinking response. Both effects were 100% blockable by [Sar1,Thr8]-AII pretreatment. Predictably, an aminopeptidase inhibitor, bestatin, greatly elongated the half-lives of AII and AIII in the cerebroventricles. Since neither of these treatments included the introduction of exogenous angiotensins, we have concluded that perturbations of the endogenous brain-angiotensin system are effective at rapidly influencing both cardiovascular and body fluid homeostasis, thus highlighting the paramount role played by brain angiotensin in their ongoing regulation.

Aminopeptidases↗

PubMedDate not supplied

Mannitol and dextran increase cochlear blood flow in normotensive and spontaneously hypertensive rats.

Pharmacologic treatments for otopathologies of possible vascular origin are aimed at enhancing vascular transport and are intended to increase cochlear blood flow (CBF). In the current study, normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs) were given intravascular infusions of mannitol (20%), dextran 70 (6%), or control saline. In general, the results clearly indicate that both osmotic agents effectively increase CBF, as measured by laser Doppler flowmetry. However, the mechanism of action of these agents is less clear.

Animals↗