thiobutabarbital and Hypertension

This study was designed to test whether previous work, which showed that the angiotensin converting enzyme (ACE) inhibitor enalaprilat potentiated the alpha 1-adrenoceptor antagonist activity of doxazosin in isolated rat tail arteries, could be extended to demonstrate a synergistic hypotensive effect of these two drugs.. Groups of untreated or chronically deoxycorticosterone acetate (DOCA)-salt-treated female Sprague-Dawley rats were used. Rats were anaesthetized with Inactin (barbiturate); drugs were administered via a jugular venous catheter; blood pressure was monitored via a carotid arterial catheter.. In previously untreated rats, pretreatment with enalaprilat shifted the dose-response curve for the hypotensive effect of doxazosin to the left, indicating synergism. In rats dosed with DOCA-salt (which suppresses renin and angiotensin II production): (1) there was no synergism between the hypotensive actions of enalaprilat and doxazosin; (2) doxazosin was more potent than in untreated rats; and (3) enalaprilat lowered blood pressure, suggesting a hypotensive mechanism separate from ACE inhibition.. In the absence of angiotensin II (resulting from enalaprilat administration or from chronic DOCA-salt), doxazosin had a greater hypotensive action than in the presence of angiotensin II. This is consistent with the concept that angiotensin II modulates alpha 1-adrenoceptor activity.

Topics: Anesthesia; Animals; Antihypertensive Agents; Desoxycorticosterone; Disease Models, Animal; Dose-Response Relationship, Drug; Doxazosin; Drug Evaluation, Preclinical; Drug Interactions; Enalaprilat; Female; Hypertension; Prazosin; Rats; Rats, Inbred Strains; Thiopental

Open-loop tubulo-glomerular feedback (TGF) responses were measured in halothane anaesthetized spontaneously hypertensive rats (SHR), in normotensive Wistar Kyoto (WKY) and Sprague-Dawley rats (SPRD), and in inactin anaesthetized SPRD. Proximal intratubular free flow pressures (FFP) (13.8-14.7 mm Hg) and stop-flow pressures (40.0-42.4 mm Hg) were similar in the four groups, but systemic arterial pressure was significantly lower in WKY, and significantly higher in SHR than in SPRD. The turning point (Tp) of the feedback curve was 9.87 nl/min in SHR, significantly lower than the 13.04 nl/min found in WKY. Maximum TGF pressure response was 28.6% greater in SHR than in the normotensive rats (13.3 vs. 9.5 mm Hg; p less than 0.025). The sensitivity, as estimated from the slope of the feedback curve at the Tp [f'(Tp)] was 87% greater in SHR than in WKY. There was no significant difference between these parameters in WKY and SPRD. The TGF pressure response was biphasic in the 3 groups of halothane anaesthetized rats with a steady state level reached in about 2 min after the change in late proximal microperfusion rate. In inactin anaesthetized rats the sensitivity was 41% lower than in the halothane anaesthetized control group of SPRD, the feedback response was lower, and the feedback curve was displaced to the right with the Tp at 15.9 nl/min, significantly higher than in the control group (p less than 0.001). Although the steady state level also was reached within 2 min, the clearly biphasic pattern of the pressure response was less consistent.

Topics: Animals; Blood Flow Velocity; Blood Pressure; Feedback; Halothane; Hypertension; Kidney Glomerulus; Kidney Tubules, Proximal; Male; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Thiopental

Proximal tubular compliance (C) was measured in free flow microperfusion experiments from the initial slope of the increase in proximal luminal pressure divided by the step input of volume flow delivered from a microperfusion pipette inserted in a downstream proximal convolution. Five groups of rats were studied: Munich Wistar (WU, n = 11) and Sprague-Dawley rats (SPRD, n = 6) anaesthetized with inactin; and SPRD (n = 11), Wistar Kyoto (WKY, n = 9), and spontaneously hypertensive rats (SHR, n = 11) anaesthetized with halothane. In the inactin groups, C was: 0.309 +/- 0.161 and 0.266 +/- 0.136 nl mm Hg-1, respectively. In the halothane groups, C was: 0.125 +/- 0.023, 0.125 +/- 0.029, and 0.119 +/- 0.0127 nl mm Hg-1, respectively. The means in the inactin groups were significantly higher than those from the halothane groups (P less than 0.001). It is concluded that the choice of anaesthetics has a profound influence on the proximal tubular compliance in the rat, and that the compliance of SHR is equal to that of normotensive rats.

Topics: Anesthesia, Inhalation; Animals; Compliance; Halothane; Hypertension; Kidney Tubules, Proximal; Male; Nitrous Oxide; Perfusion; Pressure; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Thiopental