Evidence of a shared mechanism of vasoconstriction in pulmonary and systemic circulation in hypertension: a possible role of intracellular calcium.

Abstract

SUMMARY We investigated the hemodynamics of the greater and lesser circulation in 35 patients with primary hypertension, as well as the effects of calcium-channel blockade, to test whether a common factor may account for the excessive vascular resistance in the two circuits and whether intracellular calcium concentration ([Ca++]i) may be involved. We proved that (1) elevated pulmonary arteriolar resistance (PAR) is not related to pulmonary blood flow and volume, pleural pressure, arterial oxygen or carbon dioxide tension and pH, left ventricular filling pressure and function; (2) systemic vascular resistance (SVR) significantly correlates with PAR; (3) calcium-channel blockade with nifedipine reduces systemic and pulmonary arterial pressures toward normal and significantly lowers both SVR and PAR; (4) the percent decrease in vascular resistance after nifedipine is related to the baseline level of resistance in both the greater and the lesser circulations.Failure of the mechanisms currently indicated as responsible for pulmonary vasoconstriction to explain convincingly the increased PAR, the correlation between SVR and PAR, as well as the qualitatively similar response to calcium-channel blockade suggest that a common factor produces vasoconstriction in the two circuits. A pathogenetic role of a primary disorder in [Ca++]i cannot be excluded, but remains to be proved.BLOOD PRESSURE elevation in most patients with chronic hypertension is associated with increased peripheral vascular resistance, which is due in part to abnormal constriction of the resistance vessels.' For a time, the autoregulatory theory4 was popular. Interest has now focused on the hypothesis that an excessive intracellular calcium-ion concentration ([Ca++] hypertension, these disorders are spread throughout the body and involve arteriolar smooth muscle, which is the actual culprit. Unfortunately, blood cells, which can be easily studied, are not related at all to the muscles of the vessel wall, and the theory of abnormal membrane cation transport, although attractive, will remain speculative, until more is known about the metabolism of this tissue in essential hypertension. Based on previous observations'8 -20 that pressure and arteriolar resistance in the pulmonary circulation are increased in systemic high blood pressure, we decided to investigate the hemodynamics of the lesser circulation in hypertension to determine whether there is a common factor that accounts for the vasoconstriction that involves the two circuits and whether intracellular calcium is involved.

Leptin-Induced Endothelium-Independent Vasoconstriction in Thoracic Aorta and Pulmonary Artery of Spontaneously Hypertensive Rats: Role of Calcium Channels and Stores

“…In this study, the altered response to leptin was attributed to the pulmonary endothelial dysfunction present in SHR [10]. However, already in 1989, Guazzi and associates demonstrated that, in hypertension, the pulmonary and systemic circulations shared joint mechanisms of vasoconstriction directly related to increased calcium in vascular smooth muscle cells [11]. Cytosolic calcium concentration is directly coupled to smooth muscle contraction.…”

Pulmonary vascular overreactivity in systemic hypertension. A pathophysiological link between the greater and the lesser circulation.

“…The causes of this abnormal vasomotion have not been elucidated, and no convincing explanation has been derived from the analysis of the mechanisms that are commonly indicated as interfering with the pulmonary vasomotility in humans, 14 such as changes in the respiratory gases and pH of the blood, pleural pressure, blood volume and flow through the lungs, or in the function of the left side of the heart and the related backward influences. These reasons, and the positive correlation existing between systemic and pulmonary vascular resistance, have suggested that a common factor responsible for vasoconstriction may be at work in the pulmonary and systemic circulation in hypertension.…”

Pulmonary vasoreactivity in spontaneously hypertensive rats - Effects of endothelin-1 and leptin

“…Indeed, healthy aortic endothelium negatively regulates α1-agonists- and endothelin-1-induced contraction through a basal endothelial NO release [33-35], which is partly lost in spontaneously hypertensive rats [36-38]. The imbalance between NO and endothelin-1 signaling pathways may, at least, partially mediate pulmonary endothelial dysfunction in this hypertensive strain, together with previously described altered calcium handling [2]. Even if we found some similar pathobiological anomalies within the pulmonary circulation of SHR compared to those observed in PAH patients, there is no clear evidence that these two conditions share common early pathogenic mechanisms.…”

“…Guazzi et al hypothesized that this would be related to shared abnormal smooth muscle calcium handling mechanisms in the systemic and pulmonary resistive vessels [2]. In support of this notion, these authors reported an enhanced pulmonary vascular reactivity to hypoxia in patients with uncomplicated systemic hypertension [3].…”