This review provides a brief summary of molecular and pathophysiological events involved in the development and reversal of hypertensive left ventricular hypertrophy (LVH). Data gathered in our laboratory over the years are emphasized. Since ventricular hypertrophy confers considerable risk for increased premature cardiovascular morbidity and mortality, particular atttention has been given to reversal of hypertrophy and those factors that may determine the outcome of the reversal process. Our data show that reversal of hypertrophy and ventricular function postregression depend not only on hemodynamic factors but also on nonhemodynamic factors. Thus, various antihypertensive agents have demonstrated differences in their ability to promote LVH reversal and affect ventricular function. The possible roles of the local myocytic renin-angiotensin system, alterations in calcium metabolism, accumulation of collagen and changes in coronary circulation that accompany LVH in determining ventricular function and the magnitude of risk associated with LVH are discussed. Finally, a brief overview of molecular mechanisms that mediate alterations in gene expression and initiation of growth after hemodynamic stress is given. (Hypertens Res 1993; 16: 163-177)

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To examine whether milk factors play a role in the development of hypertension in the spontaneously hypertensive rat (SHR) of the Okamoto strain we have examined the levels of electrolytes and the amino acid taurine in milk from nursing SHR, Wistar Kyoto (WKY) and the stroke prone substrain of the SHR (SHR-SP). The Na⁺ concentration of SHR milk was significantly higher than that of the WKY and SHR-SP. The K⁺ concentration of SHR milk tended to be lower than that of WKY and SHR-SP and thus the Na/K ratio of SHR milk was significantly higher than that of both the SHR-SP and WKY. While taurine levels of SHR and SHR-SP milk were 29% and 28% higher than that of WKY respectively, these differences were only of borderline significance (p=0.07). The blood pressure of offspring at 8 and 12 weeks failed to correlate with milk factors within any strain. Thus while the altered levels of electrolytes in milk from SHR may play a role in the development of its hypertension the results for the SHR-SP suggests that these differences are not invariably associated with high blood pressure. (Hypertens Res 1993; 16: 179-184)

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This study was designed to elucidate the abnormalities in both the parasympathetic and sympathetic nervous systems in borderline hypertension. Utilizing the cold pressor test (CPT) for evaluation of the sympathetic nervous system and R-R interval variation for the assessment of the parasympathetic nervous system, fifteen male patients (37±4 y.o.) with borderline hypertension (mean arterial pressure=111±2mmHg) and age-matched normotensive controls participated in this study. The cold face test (CFT), which is able to evaluate the trigeminal-vagal-cardiac and trigeminal-sympathetic-peripheral vasculature pathways, was also employed to evaluate the balance between these two divisions of the autonomic nervous system. The coefficient of variation (CV) of R-R interval variation in the borderline hypertensives was significantly smaller than that in the controls (3.9±0.3vs. 6.3±0.4%, P<0.01). The CPT produced a significant elevation of blood pressure in both groups, but there were no significant differences between the two groups. The CFT induced bradycardia (P<0.01) in the controls, while hypertensive subjects were characterized by an increase in systolic blood pressure (P<0.01) without significant changes in heart rate. Epinephrine was significantly decreased by the CFT only in the controls. There was a positive correlation between CV of R-R interval and decrease in heart rate by the CFT (r=0.60, P<0.0005). These results suggest that even with a specifically vagal reflex, patients with borderline hypertension have decreased parasympathetic tone and that the CFT may be useful in the assessment of the balance between the sympathetic and parasympathetic nervous systems over the regulation of the effector organs. (Hypertens Res 1993; 16: 185- 190)

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To elucidate the clinical significance of negative T wave on electrocardiogram in patients with essential hypertension, the relation between negative T wave and left ventricular mass (LVM) was studied in 89 patients with essential hypertension. Left ventricular hypertrophy was defined as an LVM index of equal to or greater than 125g/m². Essential hypertensive patients were classified into the following three groups: Group I (n=46) with neither left ventricular hypertrophy nor a history of hypertensive heart failure, Group II (n=33) with left ventricular hypertrophy and without a history of hypertensive heart failure, and Group III (n=10) with both left ventricular hypertrophy and a history of hypertensive heart failure. Negative T waves in essential hypertensive patients were observed in 4.3% of Group I, 51.5% of Group II and 100% of Group III. LVM indices in Groups I, II and III were 97±18(g/m²), 151±20 (p<0.01vs. I) and 238±23 (p<0.01vs. II), respectively. There was a significant relationship between the depth of negative T wave and LVM index (r=0.61, p<0.001). However, there was no significant difference in LVM index between Group II with negative T wave and without negative T wave. Essential hypertensive patients with more than 190g/m² of LVM index developed hypertensive heart failure. These findings indicate that the negative T wave and its depth in patients with essential hypertension correlate well with LVM, but myocardial injury and ischemia associated with ventricular hypertrophy also have some influences on the appearance of negative T wave. (Hypertens Res 1993;16: 191-195)

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This study is based on a representative population sample of women in Gothenburg, Sweden. Three hundred and thirty-six 50-year-old nondiabetic women, not taking any antihypertensive medication, were included in the study. They underwent a comprehensive examination programme, where body weight, body height, waist and hip circumferences, systolic and diastolic blood pressures and fasting serum insulin concentration were measured. Fasting serum insulin concentration was significantly correlated with systolic and diastolic blood pressures. After controlling for both body mass index (BMI) and waist to hip circumference ratio (WHR), fasting serum insulin concentration remained independently associated with blood pressure (P=0.001 for systolic blood pressure, P=0.06 for diastolic blood pressure). When stratified for BMI or WHR the correlations between fasting serum insulin concentration and blood pressure remained significant only in the upper 50th precentiles of BMI and WHR. When relating pressure to different levels of fasting serum insulin concentration there seems to be a threshold at an insulin concentration corresponding to the upper quartile limit (at approximately 17μU/ml), above which level the blood pressure rises more obviously. The same phenomenon was seen for systolic and diastolic blood pressures. (Hypertens Res 1993; 16: 197-201)

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The spontaneously hypertensive rat (SHR) is a commonly used model of human essential hypertension. Several factors have been correlated with this hypertension but little attention has been focused on any oral manifestations that may be present. Following sacrifice of SHR, WKY or Sprague-Dawley rats, aged 6 months, mandibles were dissected out and defleshed in a concentrated papain solution. Measurements were made in each hemimandible of tooth loss, crown height and bone loss. SHR were significantly more susceptible to tooth loss than either the WKY or Sprague-Dawley strains. In SHR, decreased crown height and increased bone loss were significant when compared to the normotensive controls. The mechanism for the tooth loss remains to be elucidated, but may involve lowered calcium, immune deficiency and/or overactive sympathetic activity. Many hypertensive patients are seen routinely in dental offices, and little attention is given to any special conditions that may exist in the oral cavities of these patients. These results suggest a link between hypertension and oral disease and point to the SHR as a model for further study of the connection between these two disease states. (Hypertens Res 1993;16: 203-208)

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The relationship between sleep apnea and blood pressure was examined in 7 patients with sleep apnea syndrome (SAS). In addition, whether or not SAS is a risk factor for cerebrovascular disease was assessed. Polysomnography, including measurements of arterial O₂ saturation (SaO₂), was performed in 7 patients during a 3-day hospitalization period; direct intra-arterial blood pressure was continuously recorded. The blood pressure data were analyzed at the beginning of apnea, the beginning of fall in SaO₂, the end of apnea, the time of maximum blood pressure, and the time of SaO₂ recovery. Analysis was also carried out for 30s at 30-min intervals to assess nocturnal blood pressure variability. Two urine specimens, one accumulated from 9 a.m. to 9 p.m. and the other from 9 p.m. to 9 a.m., were collected. The pattern of blood pressure changes did not reveal the nocturnal decrease observed in normal subjects. A transient elevation of blood pressure was observed at the end of each apneic period; the mean increase in blood pressure was 28.0mmHg in systole and 16.4mmHg in diastole, and the maximum increase in systolic blood pressure was over 100mmHg. There was no significant difference between diurnal and nocturnal concentrations of urinary catecholamines, suggesting that the sympathetic activity of patients with SAS is not decreased at night. Furthermore, the transient but considerable elevation of blood pressure observed at the end of each apneic period suggests that SAS may potentially trigger cerebrovascular disease. (Hypertens Res 1993;16: 209-213)

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Endothelin (ET) isopeptide and receptor subtype are distributed in various tissues, suggesting diverse functions as local factors other than acting as potent vasoconstrictors. We have studied whether ET Isopeptide and receptor subtype are concomitantly expressed in pheochromocytoma and bovine adrenal medulla by binding studies and Northern blot analysis and compared the results with those in human and bovine adrenal cortex. Binding studies using [¹²⁵I]ET-1 as a radioligand revealed a single class of high-affinity binding sites for ET-1 in membranes from two pheochromocytomas and normal bovine adrenal medulla, which were almost comparable to those from human and bovine adrenal cortex. ET-1 and ET-2 equipotently and competitively inhibited [¹²⁵I]ET-1 binding to the membranes, whereas ET-3 was far less potent than ET-1 at higher concentrations, suggesting heterogeneous subpopulations of ET receptors. Northern blot analysis using cDNAs for ET_A and ET_B receptors revealed that both ET_A and ET_B receptor mRNAs are expressed in pheochromocytoma and bovine adrenal medulla in a similar fashion as in human and bovine adrenal cortex. Northern blot analysis using cDNAs for human preproET-1 and preproET-3 as probes also revealed the concomitant expression of preproET-1 mRNA in pheochromocytoma and bovine adrenal medulla and preproET-3 mRNA in human adrenal cortex. These data demonstrate for the first time that ET receptor subtype (ET_A and ET_B) and ET isopeptide (ET-1 and ET-3) are concomitantly expressed by pheochromocytoma as well as bovine adrenal medulla, suggesting the paracrine/autocrine function of ET in adrenomedullary chromaffin cells. (Hypertens Res 1993;16: 215-219)

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A case of renovascular hypertension with localized ischemia in the left kidney is described. The captopril test and renography showed a pattern typical of renin-dependent unilateral renovascular hypertension. However, renal arteriography did not show stenosis of the renal artery. Enhanced and dynamic computed tomography revealed ischemia in the dorsal portion of the left kidney and an aortic dissection with thrombosis, suggesting obstruction of the supplemental renal artery of double renal arteries. The localized renal ischemia was attributed to insufficient blood supply from the main renal artery to the obstructed area.(Hypertens Res 1993; 16: 221-224)

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