dihydropyridines and Hypertension--Malignant

1. In order to evaluate the therapeutic effects of antihypertensive agents on malignant hypertension in M-SHRSP, EEG were performed as a non-invasive, therapeutic index. 2. Under pentobarbital anaesthesia, the EEG pattern of rats with severe hypertension and/or cerebrovascular lesions showed alternate short-active and long-depressive phases with spike and sharp waves. 3. When M-SHRSP were treated with an angiotensin converting enzyme inhibitor (SQ 29,852) or a calcium antagonist (manidipine), the depressive phases became shorter and active phases longer. These changes were more prominent in manidipine treated rats than in SQ 29,852 treated rats. 4. The EEG spike- and sharp-wave complex seems to be a convenient index for evaluating cerebrovascular lesions and cerebral activity in M-SHRSP.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Body Weight; Calcium Channel Blockers; Dihydropyridines; Electroencephalography; Hypertension, Malignant; Longevity; Male; Nitrobenzenes; Organophosphorus Compounds; Piperazines; Proline; Rats; Rats, Inbred SHR

To examine the pathogenetic role of platelet-derived growth factor (PDGF) in hypertensive kidney damage, we studied the gene expression of PDGF A-chain and B-chain in an animal model of malignant hypertension. Experimental malignant hypertension induced by unilateral nephrectomy combined with deoxycorticosterone and salt loading in the spontaneously hypertensive rat resulted in severely elevated blood pressure and renal histological damage, characterized by necrotizing vasculitis. Using reverse transcription-polymerase chain reaction analysis followed by Southern blot analysis, we observed that PDGF B-chain gene expression was increased in the kidney of experimental malignant hypertension and was correlated with the severity of glomerular damage, while PDGF A-chain gene expression was unaffected. Antihypertensive treatment with manidipine reduced glomerular damage and a decreased gene expression of PDGF B-chain. These results suggest that PDGF B-chain may have a role in mediating hypertensive kidney damage.

Topics: Animals; Base Sequence; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Disease Models, Animal; Gene Expression; Hypertension, Malignant; Kidney; Molecular Sequence Data; Nitrobenzenes; Piperazines; Platelet-Derived Growth Factor; Polymerase Chain Reaction; Rats; Rats, Inbred SHR; RNA-Directed DNA Polymerase

The aim of this study was to characterize the antihypertensive and vasoprotective properties of lacidipine in salt-loaded Dahl-S rats, a suitable animal model of malignant hypertension. After 9 weeks of a high (8%) sodium chloride (NaCl) diet, 80% of the untreated Dahl-S rats died (20% survival rate) whereas a 100% survival rate was observed with chronic treatment with lacidipine at doses of 0.1 (equivalent to the recommended dose in humans), 0.3, 1, and 10 mg/kg once daily by gastric gavage. The most interesting results included the following: (a) Only the highest dose tested (10 mg/kg once daily) was able to control the increase in blood pressure, which was measured 24 h after the preceding administration of drug, yet a 100% survival rate was maintained. (b) There appeared to be prevention of brain lesions, which is very likely the cause of the survival of all of the lacidipine-treated rats in this study. (c) A clear dose-related vascular protection was observed in other tissues. In conclusion, lacidipine protects against the vascular damage and concomitant increase in mortality of salt-loaded Dahl-S rats even at doses that do not adequately control the development of hypertension.

Topics: Administration, Oral; Animals; Blood Pressure; Brain; Calcium Channel Blockers; Dihydropyridines; Disease Models, Animal; Fundus Oculi; Hypertension, Malignant; Male; Myocardium; Organ Size; Rats; Rats, Inbred SHR; Sodium, Dietary