TY - JOUR

T1 - Angiotensin II receptor antagonist CV-11974 and cerebral blood flow autoregulation

AU - Vraamark, T

AU - Waldemar, G

AU - Strandgaard, S

AU - Paulson, O B

PY - 1995/7

Y1 - 1995/7

N2 - OBJECTIVE: To investigate whether the angiotensin II (Ang II) subtype 1 receptor (AT1) antagonist CV-11974 had a similar effect to angiotensin converting enzyme inhibitors on cerebral blood flow autoregulation in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).METHODS: Sixteen WKY rats and 16 SHR were given CV-11974 0.1 mg/kg intravenously and compared with two control groups (n = 16). Their cerebral blood flow was measured with the intracarotid xenon-133 injection method and blood pressure was raised by noradrenaline infusion and lowered by controlled haemorrhage in separate groups of rats. The limits of autoregulation were determined by computed least-sum-of-squares analysis.RESULTS: The dose of CV-11974 given lowered blood pressure but did not influence baseline cerebral blood flow. In WKY rats the lower limit of autoregulation in control rats was 60 +/- 3 mmHg, whereas after CV-11974 administration it was 48 +/- 2 mmHg (P < 0.01). In SHR the corresponding values were 85 +/- 2 and 78 +/- 2 mmHg, respectively (P < 0.05). In WKY rats the upper limit of autoregulation in control rats was 144 +/- 5 mmHg, whereas after CV-11974 administration it was 126 +/- 7 mmHg (P < 0.05). In SHR the corresponding figures were 174 +/- 8 and 144 +/- 6 mmHg, respectively (P < 0.01).CONCLUSION: Thus, the AT1 receptor antagonist, although it did not influence baseline cerebral blood flow, shifted the autoregulation curve towards lower blood pressure. This effect is similar to that of angiotensin converting enzyme inhibitors, and might be due to release of Ang II-dependent tone in the larger cerebral resistance vessels.

AB - OBJECTIVE: To investigate whether the angiotensin II (Ang II) subtype 1 receptor (AT1) antagonist CV-11974 had a similar effect to angiotensin converting enzyme inhibitors on cerebral blood flow autoregulation in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).METHODS: Sixteen WKY rats and 16 SHR were given CV-11974 0.1 mg/kg intravenously and compared with two control groups (n = 16). Their cerebral blood flow was measured with the intracarotid xenon-133 injection method and blood pressure was raised by noradrenaline infusion and lowered by controlled haemorrhage in separate groups of rats. The limits of autoregulation were determined by computed least-sum-of-squares analysis.RESULTS: The dose of CV-11974 given lowered blood pressure but did not influence baseline cerebral blood flow. In WKY rats the lower limit of autoregulation in control rats was 60 +/- 3 mmHg, whereas after CV-11974 administration it was 48 +/- 2 mmHg (P < 0.01). In SHR the corresponding values were 85 +/- 2 and 78 +/- 2 mmHg, respectively (P < 0.05). In WKY rats the upper limit of autoregulation in control rats was 144 +/- 5 mmHg, whereas after CV-11974 administration it was 126 +/- 7 mmHg (P < 0.05). In SHR the corresponding figures were 174 +/- 8 and 144 +/- 6 mmHg, respectively (P < 0.01).CONCLUSION: Thus, the AT1 receptor antagonist, although it did not influence baseline cerebral blood flow, shifted the autoregulation curve towards lower blood pressure. This effect is similar to that of angiotensin converting enzyme inhibitors, and might be due to release of Ang II-dependent tone in the larger cerebral resistance vessels.

KW - Angiotensin II/antagonists & inhibitors

KW - Angiotensin Receptor Antagonists

KW - Animals

KW - Benzimidazoles/pharmacology

KW - Blood Pressure/drug effects

KW - Cerebrovascular Circulation/drug effects

KW - Homeostasis/drug effects

KW - Hypertension/physiopathology

KW - Male

KW - Rats

KW - Rats, Inbred SHR

KW - Rats, Inbred WKY

KW - Tetrazoles/pharmacology

M3 - Journal article

C2 - 7594439

VL - 13

SP - 755

EP - 761

JO - Journal of Hypertension, Supplement

JF - Journal of Hypertension, Supplement

SN - 0952-1178

IS - 7

ER -