Prostaglandins but not nitric oxide protect renal medullary perfusion in anaesthetised rats receiving angiotensin II

Abstract

Angiotensin II (Ang II) fails to constrict renal medullary vasculature, possibly due to the counteraction of local vasodilators, such as prostaglandins or nitric oxide (NO). The effects of exogenous Ang II on intrarenal circulation were determined in anaesthetised rats that were untreated or pretreated with indomethacin (Indo) or L-NAME. The total renal blood flow (RBF), representing cortical perfusion, and outer and inner medullary blood flow (OMBF and IMBF) were measured. In untreated rats, Ang II decreased RBF in a dose dependent manner. Intravenous administration of 30 ng kg-1 min-1 Ang II decreased RBF by 38 % and OMBF by 9 % (both significant); IMBF was unaffected. Indo (5 mg kg-1 I.V.) significantly and similarly decreased OMBF and IMBF without affecting RBF. Ang II decreased IMBF by 27 % in Indo-pretreated rats, but caused no change in rats without pretreatment. The decreases in OMBF and RBF were comparable with or without Indo pretreatment. Inhibition of NO synthesis with L-NAME (0.6 mg kg-1 I.V.) significantly decreased RBF, OMBF and IMBF. Ang II infusion into L-NAME-pretreated rats induced a further significant decrease in RBF and OMBF without changing IMBF. We conclude that within the inner medulla, but not the outer medulla or cortex, prostaglandins effectively counteract the vasopressor effect of circulating Ang II.

Figure 1. Effects of three doses of angiotensin II (ANG II) on total renal blood flow (RBF) and outer and inner medullary blood flow (OMBF and IMBF)

Means ±s.e.m. are shown as percentages of the initial control value (100 %). Absolute mean values in ml min⁻¹ (RBF) and perfusion units (OMBF and IMBF) are shown on the bars. Numbers (n) are given in parentheses. * Significantly different from 100 % control value at P < 0.05.

Figure 2. Effects of Indo and of infusion of Ang II given after Indo on total RBF, OMBF and IMBF

░, Indo (5 mg kg⁻¹i.v.); ▪, infusion of Ang II (30 ng kg⁻¹ min⁻¹i.v.) after Indo. Means ±s.e.m. are shown as a percentages of pre-Indo control (□, 100 %). Absolute mean values in ml min⁻¹ (RBF) and perfusion units (OMBF, and IMBF) are shown on the bars. Numbers (n) are given in parentheses. * Significantly different from pre-Indo control at P < 0.05; † significantly different from the value measured after Indo at P < 0.05.

Figure 3. Effects of l-NAME and of infusion of Ang II given after l-NAME on total RBF, OMBF and IMBF

░, l-NAME (0.6 mg kg⁻¹); ▪, infusion of Ang II (30 ng kg⁻¹ min⁻¹) after l-NAME. Means ±s.e.m. are shown as percentages of pre-l-NAME control (□, 100 %). Absolute mean values in ml min⁻¹ (RBF) and perfusion units (OMBF and IMBF) are shown on the bars. Numbers (n) are given in parentheses. * Significantly different from pre-l-NAME control at P < 0.05; † significantly different from the value measured after l-NAME at P < 0.05.

Figure 4. A comparison of Ang II effects on total RBF, OMBF and IMBF in control rats and animals pretreated with Indo or l-NAME

Ang II was infused at 30 ng kg⁻¹ min⁻¹. Means ±s.e.m. are percentage changes from pre-Ang II control. * Significantly different from pre-Ang II control at P < 0.05; † significantly different from the change measured after Ang II alone (Saline, □) at P < 0.05.