Ziegelhöffer-Mihalovicova Barbara, Arnold Nicole, Marx Grit, Tannapfel Andrea, Zimmer Heinz-Gerd, Rassler Beate
Carl-Ludwig-Institute of Physiology, University of Leipzig, Liebigstr. 27 04103 Leipzig, Germany.
Life Sci. 2006 Jul 24;79(9):838-46. doi: 10.1016/j.lfs.2006.02.041. Epub 2006 Mar 28.
We investigated the effects of salt loading on blood pressure, cardiac hypertrophy and fibrosis as well as on the effectiveness of various antihypertensive therapies in young spontaneously hypertensive rats (SHR). Twenty-five male SHR were salt-stimulated by drinking 1% NaCl from 3 to 6 months of age. Eighteen of them were treated for the last 2 weeks of salt loading with either the angiotensin-converting enzyme inhibitor captopril, the beta-adrenergic receptor blocker propranolol or the calcium-channel antagonist verapamil. Age-matched male Wistar-Kyoto (WKY) rats and SHR drinking only water served as controls. At the age of 6 months, SHR had significantly elevated blood pressure that was unchanged by salt loading. Relative heart weight was increased in SHR without (3.3) and even more so with salt intake (3.6 vs. 2.4 in WKY). Left ventricular (LV) hypertrophy was accompanied by a 17-fold increase in the expression of mRNA for atrial natriuretic factor (ANF) both in untreated and salt-loaded SHR compared to WKY (p<0.001). Collagen I and III mRNA increased 1.7-1.8-fold in SHR without and with additional salt intake (p<0.01). None of the therapies significantly reduced blood pressure or hypertrophy. Although captopril had no antihypertensive effect, it reduced ANF, collagen I and III mRNA in LV to control level. Less pronounced effects were achieved with verapamil. These findings emphasize the cardioprotective role of captopril which may not be fully expressed in the presence of elevated salt intake.
我们研究了盐负荷对年轻自发性高血压大鼠（SHR）血压、心脏肥大和纤维化的影响，以及对各种抗高血压疗法疗效的影响。25只雄性SHR在3至6月龄时通过饮用1%氯化钠溶液进行盐刺激。其中18只在盐负荷的最后2周用血管紧张素转换酶抑制剂卡托普利、β-肾上腺素能受体阻滞剂普萘洛尔或钙通道拮抗剂维拉帕米进行治疗。年龄匹配的雄性Wistar-Kyoto（WKY）大鼠和只饮用纯水的SHR作为对照。6月龄时，SHR的血压显著升高，盐负荷对其无影响。未摄入盐（3.3）和摄入盐（与WKY的2.4相比为3.6）的SHR的相对心脏重量均增加。与WKY相比，未治疗和盐负荷的SHR左心室（LV）肥大均伴有心房利钠因子（ANF）mRNA表达增加17倍（p<0.001）。未摄入盐和额外摄入盐的SHR中I型和III型胶原蛋白mRNA增加1.7 - 1.8倍（p<0.01）。这些疗法均未显著降低血压或减轻肥大。虽然卡托普利没有降压作用，但它将LV中的ANF、I型和III型胶原蛋白mRNA降低至对照水平。维拉帕米的效果则不太明显。这些发现强调了卡托普利的心脏保护作用，在盐摄入量升高的情况下，这种作用可能无法完全体现出来。
