Effects of salt loading and various therapies on cardiac hypertrophy and fibrosis in young spontaneously hypertensive rats.
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.
Ziegelhöffer-Mihalovicova
Barbara
B
Carl-Ludwig-Institute of Physiology, University of Leipzig, Liebigstr. 27 04103 Leipzig, Germany.
Arnold
Nicole
N
Marx
Grit
G
Tannapfel
Andrea
A
Zimmer
Heinz-Gerd
HG
Rassler
Beate
B
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002216:Captopril / Q000627:therapeutic use; D006332:Cardiomegaly / Q000188:drug therapy* / Q000473:pathology*; D003094:Collagen / Q000096:biosynthesis; D004435:Eating / Q000502:physiology; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology*; D023282:Nuclease Protection Assays; D011433:Propranolol / Q000627:therapeutic use; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012965:Sodium Chloride / Q000494:pharmacology*; D014700:Verapamil / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D012965:Sodium Chloride; D012313:RNA; D003094:Collagen; D002216:Captopril; D011433:Propranolol; D014700:Verapamil