Altered cardiovascular regulation in arginine vasopressin-overexpressing transgenic rat

Kazushige Tachikawa, Hisashi Yokoi, Hiroshi Nagasaki, Hiroshi Arima, Takashi Murase, Yoshihisa Sugimura, Yoshitaka Miura, Masumi Hirabayashi, Yutaka Oiso

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Although arginine vasopressin (AVP), an antidiuretic hormone, has been widely acknowledged to play an important role in cardiovascular regulation via V1a receptors (V1aR), its precise significance remains unclear. In this study, we investigated the effects of long-standing high plasma AVP status on cardiovascular regulation in the AVP-overexpressing transgenic (Tg) rat. Adult male homozygous Tg rats were compared with age-matched normal Sprague-Dawley rats as controls. There were no significant differences in mean arterial blood pressure (BP; MABP) or heart rate between Tg and control rats in the basal state. Subcutaneous injection of AVP significantly increased MABP in controls but did not cause any apparent increase in MABP in Tg rats. BP recovery from hemorrhage-induced hypotension was significantly delayed in Tg compared with control rats. Pretreatment with a selective V1aR antagonist, OPC-21268, which is thought to restore the downregulation of V1aR, markedly improved both of these impaired responses. Northern blot analysis confirmed that decreased expression of V1aR mRNA and pretreatment with V1aR antagonist significantly restored the downregulation of V1aR mRNA. These results suggest that the Tg rat has decreased sensitivity to the hypertensive effect of AVP due to downregulation of V1aR, which may function as an adaptive mechanism to maintain normal BP against chronic hypervasopressinemia. In addition, impaired restoration of BP after hemorrhage-induced hypotension in Tg rats supports a physiological role of AVP in cardiovascular regulation.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume285
Issue number6 48-6
Publication statusPublished - 01-12-2003

Fingerprint

Transgenic Rats
Arginine Vasopressin
Controlled Hypotension
OPC 21268
Down-Regulation
Arterial Pressure
Hemorrhage
Messenger RNA
Subcutaneous Injections
Vasopressins
Northern Blotting
Sprague Dawley Rats
Heart Rate

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Tachikawa, Kazushige ; Yokoi, Hisashi ; Nagasaki, Hiroshi ; Arima, Hiroshi ; Murase, Takashi ; Sugimura, Yoshihisa ; Miura, Yoshitaka ; Hirabayashi, Masumi ; Oiso, Yutaka. / Altered cardiovascular regulation in arginine vasopressin-overexpressing transgenic rat. In: American Journal of Physiology - Endocrinology and Metabolism. 2003 ; Vol. 285, No. 6 48-6.
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abstract = "Although arginine vasopressin (AVP), an antidiuretic hormone, has been widely acknowledged to play an important role in cardiovascular regulation via V1a receptors (V1aR), its precise significance remains unclear. In this study, we investigated the effects of long-standing high plasma AVP status on cardiovascular regulation in the AVP-overexpressing transgenic (Tg) rat. Adult male homozygous Tg rats were compared with age-matched normal Sprague-Dawley rats as controls. There were no significant differences in mean arterial blood pressure (BP; MABP) or heart rate between Tg and control rats in the basal state. Subcutaneous injection of AVP significantly increased MABP in controls but did not cause any apparent increase in MABP in Tg rats. BP recovery from hemorrhage-induced hypotension was significantly delayed in Tg compared with control rats. Pretreatment with a selective V1aR antagonist, OPC-21268, which is thought to restore the downregulation of V1aR, markedly improved both of these impaired responses. Northern blot analysis confirmed that decreased expression of V1aR mRNA and pretreatment with V1aR antagonist significantly restored the downregulation of V1aR mRNA. These results suggest that the Tg rat has decreased sensitivity to the hypertensive effect of AVP due to downregulation of V1aR, which may function as an adaptive mechanism to maintain normal BP against chronic hypervasopressinemia. In addition, impaired restoration of BP after hemorrhage-induced hypotension in Tg rats supports a physiological role of AVP in cardiovascular regulation.",
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Tachikawa, K, Yokoi, H, Nagasaki, H, Arima, H, Murase, T, Sugimura, Y, Miura, Y, Hirabayashi, M & Oiso, Y 2003, 'Altered cardiovascular regulation in arginine vasopressin-overexpressing transgenic rat', American Journal of Physiology - Endocrinology and Metabolism, vol. 285, no. 6 48-6.

Altered cardiovascular regulation in arginine vasopressin-overexpressing transgenic rat. / Tachikawa, Kazushige; Yokoi, Hisashi; Nagasaki, Hiroshi; Arima, Hiroshi; Murase, Takashi; Sugimura, Yoshihisa; Miura, Yoshitaka; Hirabayashi, Masumi; Oiso, Yutaka.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 285, No. 6 48-6, 01.12.2003.

Research output: Contribution to journalArticle

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AU - Tachikawa, Kazushige

AU - Yokoi, Hisashi

AU - Nagasaki, Hiroshi

AU - Arima, Hiroshi

AU - Murase, Takashi

AU - Sugimura, Yoshihisa

AU - Miura, Yoshitaka

AU - Hirabayashi, Masumi

AU - Oiso, Yutaka

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